General anesthesia is widely applied in clinical practice.However,the precise mechanism of loss of consciousness induced by general anesthetics remains unknown.Here,we measured the dynamics of five neurotransmitters,i...General anesthesia is widely applied in clinical practice.However,the precise mechanism of loss of consciousness induced by general anesthetics remains unknown.Here,we measured the dynamics of five neurotransmitters,includingγ-aminobutyric acid,glutamate,norepinephrine,acetylcholine,and dopamine,in the medial prefrontal cortex and primary visual cortex of C57BL/6 mice through in vivo fiber photometry and genetically encoded neurotransmitter sensors under anesthesia to reveal the mechanism of general anesthesia from a neurotransmitter perspective.Results revealed that the concentrations of γ-aminobutyric acid,glutamate,norepinephrine,and acetylcholine increased in the cortex during propofol-induced loss of consciousness.Dopamine levels did not change following the hypnotic dose of propofol but increased significantly following surgical doses of propofol anesthesia.Notably,the concentrations of the five neurotransmitters generally decreased during sevoflurane-induced loss of consciousness.Furthermore,the neurotransmitter dynamic networks were not synchronized in the non-anesthesia groups but were highly synchronized in the anesthetic groups.These findings suggest that neurotransmitter dynamic network synchronization may cause anesthetic-induced loss of consciousness.展开更多
Non-invasive cerebral neuromodulation technologies are essential for the reorganization of cerebral neural networks,which have been widely applied in the field of central neurological diseases,such as stroke,Parkinson...Non-invasive cerebral neuromodulation technologies are essential for the reorganization of cerebral neural networks,which have been widely applied in the field of central neurological diseases,such as stroke,Parkinson’s disease,and mental disorders.Although significant advances have been made in neuromodulation technologies,the identification of optimal neurostimulation paramete rs including the co rtical target,duration,and inhibition or excitation pattern is still limited due to the lack of guidance for neural circuits.Moreove r,the neural mechanism unde rlying neuromodulation for improved behavioral performance remains poorly understood.Recently,advancements in neuroimaging have provided insight into neuromodulation techniques.Functional near-infrared spectroscopy,as a novel non-invasive optical brain imaging method,can detect brain activity by measuring cerebral hemodynamics with the advantages of portability,high motion tole rance,and anti-electromagnetic interference.Coupling functional near-infra red spectroscopy with neuromodulation technologies offe rs an opportunity to monitor the cortical response,provide realtime feedbac k,and establish a closed-loop strategy integrating evaluation,feedbac k,and intervention for neurostimulation,which provides a theoretical basis for development of individualized precise neuro rehabilitation.We aimed to summarize the advantages of functional near-infra red spectroscopy and provide an ove rview of the current research on functional near-infrared spectroscopy in transcranial magnetic stimulation,transcranial electrical stimulation,neurofeedback,and braincomputer interfaces.Furthermore,the future perspectives and directions for the application of functional near-infrared spectroscopy in neuromodulation are summarized.In conclusion,functional near-infrared spectroscopy combined with neuromodulation may promote the optimization of central pellral reorganization to achieve better functional recovery form central nervous system diseases.展开更多
The dichotomized brain system is a concept that was generalized from the‘dual syndrome hypothesis’to explain the heterogeneity of cognitive impairment,in which anterior and posterior brain systems are independent bu...The dichotomized brain system is a concept that was generalized from the‘dual syndrome hypothesis’to explain the heterogeneity of cognitive impairment,in which anterior and posterior brain systems are independent but partially overlap.The dopaminergic system acts on the anterior brain and is responsible for executive function,working memory,and planning.In contrast,the cholinergic system acts on the posterior brain and is responsible for semantic fluency and visuospatial function.Evidence from dopaminergic/cholinergic imaging or functional neuroimaging has shed significant insight relating to the involvement of the cerebellum in the cognitive process of patients with Parkinson’s disease.Previous research has reported evidence that the cerebellum receives both dopaminergic and cholinergic projections.However,whether these two neurotransmitter systems are associated with cognitive function has yet to be fully elucidated.Furthermore,the precise role of the cerebellum in patients with Parkinson’s disease and cognitive impairment remains unclear.Therefore,in this review,we summarize the cerebellar dopaminergic and cholinergic projections and their relationships with cognition,as reported by previous studies,and investigated the role of the cerebellum in patients with Parkinson’s disease and cognitive impairment,as determined by functional neuroimaging.Our findings will help us to understand the role of the cerebellum in the mechanisms underlying cognitive impairment in Parkinson’s disease.展开更多
BACKGROUND Cognitive dysfunction is the main manifestation of central neuropathy.Although cognitive impairments tend to be overlooked in patients with diabetes mellitus(DM),there is a growing body of evidence linking ...BACKGROUND Cognitive dysfunction is the main manifestation of central neuropathy.Although cognitive impairments tend to be overlooked in patients with diabetes mellitus(DM),there is a growing body of evidence linking DM to cognitive dysfunction.Hyperglycemia is closely related to neurological abnormalities,while often disregarded in clinical practice.Changes in cerebral neurotransmitter levels are associated with a variety of neurological abnormalities and may be closely related to blood glucose control in patients with type 2 DM(T2DM).AIM To evaluate the concentrations of cerebral neurotransmitters in T2DM patients exhibiting different hemoglobin A1c(HbA1c)levels.METHODS A total of 130 T2DM patients were enrolled at the Department of Endocrinology of Shanghai East Hospital.The participants were divided into four groups according to their HbA1c levels using the interquartile method,namely Q1(<7.875%),Q2(7.875%-9.050%),Q3(9.050%-11.200%)and Q4(≥11.200%).Clinical data were collected and measured,including age,height,weight,neck/waist/hip circumferences,blood pressure,comorbidities,duration of DM,and biochemical indicators.Meanwhile,neurotransmitters in the left hippocampus and left brainstem area were detected by proton magnetic resonance spectroscopy.RESULTS The HbA1c level was significantly associated with urinary microalbumin(mALB),triglyceride,low-density lipoprotein cholesterol(LDL-C),homeostasis model assessment of insulin resistance(HOMA-IR),and beta cell function(HOMA-β),N-acetylaspartate/creatine(NAA/Cr),and NAA/choline(NAA/Cho).Spearman correlation analysis showed that mALB,LDL-C,HOMA-IR and NAA/Cr in the left brainstem area were positively correlated with the level of HbA1c(P<0.05),whereas HOMA-βwas negatively correlated with the HbA1c level(P<0.05).Ordered multiple logistic regression analysis showed that NAA/Cho[Odds ratio(OR):1.608,95%confidence interval(95%CI):1.004-2.578,P<0.05],LDL-C(OR:1.627,95%CI:1.119-2.370,P<0.05),and HOMA-IR(OR:1.107,95%CI:1.031-1.188,P<0.01)were independent predictors of poor glycemic control.CONCLUSION The cerebral neurotransmitter concentrations in the left brainstem area in patients with T2DM are closely related to glycemic control,which may be the basis for the changes in cognitive function in diabetic patients.展开更多
T cells are essential for a healthy life,performing continuously:immune surveillance,recognition,protection,activation,suppression,assistance,eradication,secretion,adhesion,migration,homing,communications,and addition...T cells are essential for a healthy life,performing continuously:immune surveillance,recognition,protection,activation,suppression,assistance,eradication,secretion,adhesion,migration,homing,communications,and additional tasks.This paper describes five aspects of normal beneficial T cells in the healthy or diseased brain.First,normal beneficial T cells are essential for normal healthy brain functions:cognition,spatial learning,memory,adult neurogenesis,and neuroprotection.T cells decrease secondary neuronal degeneration,increase neuronal survival after central nervous system(CNS) injury,and limit CNS inflammation and damage upon injury and infection.Second,while pathogenic T cells contribute to CNS disorders,recent studies,mostly in animal models,show that specific subpopulations of normal beneficial T cells have protective and regenerative effects in seve ral neuroinflammatory and neurodegenerative diseases.These include M ultiple Sclerosis(MS),Alzheimer’s disease,Parkinson’s disease,Amyotrophic Lateral Sclerosis(ALS),stro ke,CNS trauma,chronic pain,and others.Both T cell-secreted molecules and direct cell-cell contacts deliver T cell neuroprotective,neuro regenerative and immunomodulato ry effects.Third,normal beneficial T cells are abnormal,impaired,and dysfunctional in aging and multiple neurological diseases.Different T cell impairments are evident in aging,brain tumors(mainly Glioblastoma),seve re viral infections(including COVID-19),chro nic stress,major depression,schizophrenia,Parkinson’s disease,Alzheimer’s disease,ALS,MS,stro ke,and other neuro-pathologies.The main detrimental mechanisms that impair T cell function are activation-induced cell death,exhaustion,senescence,and impaired T cell stemness.Fo urth,several physiological neurotransmitters and neuro peptides induce by themselves multiple direct,potent,beneficial,and therapeutically-relevant effects on normal human T cells,via their receptors in T cells.This scientific field is called "Nerve-Driven Immunity".The main neurotransmitters and neuropeptides that induce directly activating and beneficial effects on naive normal human T cells are:dopamine,glutamate,GnRH-Ⅱ,neuropeptide Y,calcitonin gene-related peptide,and somatostatin.Fifth, "Personalized Adoptive Neuro-Immunotherapy".This is a novel unique cellular immunotherapy,based on the "Nerve-Driven Immunity" findings,which was recently designed and patented for safe and repeated rejuvenation,activation,and improvement of impaired and dysfunctional T cells of any person in need,by ex vivo exposure of the person’s T cells to neurotransmitters and neuropeptides.Personalized adoptive neuro-immunotherapy includes an early ex vivo personalized diagnosis,and subsequent ex vivo in vivo personalized adoptive therapy,tailo red according to the diagnosis.The Personalized Adoptive Neuro-Immunotherapy has not yet been tested in humans,pending validation of safety and efficacy in clinical trials,especially in brain tumors,chronic infectious diseases,and aging,in which T cells are exhausted and/or senescent and dysfunctional.展开更多
Alzheimer’s disease(AD)is a neurodegenerative condition that disrupts nerve cell function due to the misfolding and buildup of proteins,resulting in cognitive loss and aberrant behavior.Microglia cellsare one of the ...Alzheimer’s disease(AD)is a neurodegenerative condition that disrupts nerve cell function due to the misfolding and buildup of proteins,resulting in cognitive loss and aberrant behavior.Microglia cellsare one of the crucial immune cells in the central nervous system.Depending on their activation levels,microglia cells in the degenerative phase of AD can serve either neuroprotective or neurotoxic roles.Microglia cells express several neurotransmitter receptors that play distinct functions in the degenerative progression of AD.These receptors facilitate bidirectional communication between microglia and nerve cells.The neurotransmitter receptors on microglia cells can mediate or affect the neuroprotective or toxic effects of microglia cells,thereby affecting AD pathology.This paper focuses on the gamma-aminobutyric acid,glutaminergic,cannabinoid,cholinergic,and adrenergic receptors on microglia cells and their relationship with AD.Understanding how neurotransmitter receptors on microglia function in AD will be crucial for identifying potential treatment targets.展开更多
BACKGROUND In patients with schizophrenia,the brain structure and neurotransmitter levels change,which may be related to the occurrence and progression of this disease.AIM To explore the relationships between changes ...BACKGROUND In patients with schizophrenia,the brain structure and neurotransmitter levels change,which may be related to the occurrence and progression of this disease.AIM To explore the relationships between changes in neurotransmitters,brain structural characteristics,and the scores of the Positive and Negative Symptom Scale(PANSS)in patients with first-episode schizophrenia.METHODS The case group comprised 97 patients with schizophrenia,who were evaluated using the Canadian Neurological Scale and confirmed by laboratory tests at Ningbo Mental Hospital from January 2020 to July 2022.The control group comprised 100 healthy participants.For all participants,brain structural characteristics were explored by measuring brain dopamine(DA),glutamic acid(Glu),and gamma-aminobutyric acid(GABA)levels,with magnetic resonance imaging.The case group was divided into negative and positive symptom subgroups using PANSS scores for hierarchical analysis.Linear correlation analysis was used to analyze the correlations between neurotransmitters,brain structural character istics,and PANSS scores.RESULTS Patients in the case group had higher levels of DA and lower levels of Glu and GABA,greater vertical and horizontal distances between the corpus callosum and the inferior part of the fornix and larger ventricle area than patients in the control group(P<0.05).Patients with positive schizophrenia symptoms had significantly higher levels of DA,Glu,and GABA than those with negative symptoms(P<0.05).In patients with positive schizophrenia symptoms,PANSS score was significantly positively correlated with DA,vertical and horizontal distances between the corpus callosum and the infrafornix,and ventricular area,and was significantly negatively correlated with Glu and GABA(P<0.05).In patients with negative schizophrenia symptoms,PANSS score was significantly positively correlated with DA,vertical distance between the corpus callosum and the infrafornix,horizontal distance between the corpus callosum and the infrafornix,and ventricular area,and was significantly negatively correlated with Glu and GABA(P<0.05).CONCLUSION In patients with first-episode schizophrenia,DA levels increased,Glu and GABA levels decreased,the thickness of the corpus callosum increased,and these variables were correlated with PANSS scores.展开更多
[Objectives] This study was carried out to explore the combined effects of Fu Zi(Radix Aconiti Lateralis Praeparata, the secondary root of perennial herbaceous plant Acontium carmichaeli Dehx. of family Ranunculaceae)...[Objectives] This study was carried out to explore the combined effects of Fu Zi(Radix Aconiti Lateralis Praeparata, the secondary root of perennial herbaceous plant Acontium carmichaeli Dehx. of family Ranunculaceae) and Rou Gui(Cortex Cinnamomi, the bark of Cinnamamunz cassia Presl of family Lauraceae) on intestinal neurotransmitters and microflora in rats with slow transit constipation(STC). [Methods] Experimental rats were given loperamide hydrochloride by gavage to induce STC, and then treated with Fu Zi alone, Rou Gui alone, a combination of Fu Zi and Rou Gui(2:1 w/w), and prucalopride, respectively, for 14 days. Meanwhile, the general condition, the time to first black stool and the rate of intestinal propulsion of rats in each group were observed after STC was induced and after drug treatment, and the pathological changes in rat colon were observed via hematoxylin-eosin(HE) staining, and the levels of colonic 5-hydroxytryptamine(HT), vasoactive intestinal peptide(VIP) and substance P(SP) were detected by ELISA, and the changes in intestinal flora were detected by 16S rRNA Real-time PCR. [Results] Compared with healthy rats, the time to first black stool and the rate of intestinal propulsion, colonic 5-HT and SP levels significantly decreased(p<0.01), while their colonic VIP level significantly increased(p<0.01). Compared with STC rats, the time to first black stool, the rate of intestinal propulsion, colonic 5-HT and SP levels in Fu Zi-Rou Gui(2:1) treated rats and prucalopride treated rats significantly increased(p<0.01), while their colonic VIP level significantly decreased(p<0.01). There was no significant difference in alpha diversity between healthy rats and STC rats. However, analysis on beta diversity revealed that there were differences in microflora structure and composition between them. Compared with healthy rats, the relative abundance of Firmicutes and Proteobacteria in STC rats significantly increased, while that of Bacteroidetes decreased. Compared with STC rats, the relative abundance of Proteobacteria decreased and that of Bacteroidetes and Firmicutes increased in Fu Zi-Rou Gui(2:1) treated rats;the relative abundance of Bacteroidetes and Proteobacteria decreased while that of Firmicutes increased in Fu Zi treated rats;the relative abundance of Proteobacteria decreased while that of Bacteroidetes increased in Rou Gui treated rats;the relative abundance of Firmicutes and Proteobacteria decreased while that of Bacteroidetes increased in prucalopride treated rats. The intestinal flora in rats of all groups was dominated by Lactobacillus spp. and other genera of anaerobic bacteria. Compared with healthy rats, the relative abundance of Lactobacillus spp. and Clostridium spp. in STC rats decreased, while those of Blautia spp. and Ruminococcus spp. and Allobaculum spp. increased. Compared with STC rats, the relative abundance of Lactobacillus spp. in all rats treated with drugs increased. [Conclusions] The combination of Fu Zi and Rou Gui(2:1) can effectively improve intestinal motility in STC rats by regulating intestinal microbial community and the levels of colonic neurotransmitters.展开更多
Acarbose is used to control postpran-dial blood glucose in patients with type 2 diabetes and impaired glucose tolerance,since it improves insulin re-sistance and reduces blood lipids and cardiovascular com-plications....Acarbose is used to control postpran-dial blood glucose in patients with type 2 diabetes and impaired glucose tolerance,since it improves insulin re-sistance and reduces blood lipids and cardiovascular com-plications.However,in recent years,many studies have found that acarbose can mediate and regulate a variety of neurotransmitter-related diseases,although the mech-anisms are not clear.Therefore,this paper analyzes the clinical effect of acarbose and its mediating effect on neu-rotransmitters of mental disorders through insulin,brain-gut axis,and calorie restriction,to provide a reference for the new clinical applications of acarbose.展开更多
In order to study the molecular mechanism of injury in rat organs induced by methylmercury, and the relationship between neurotransmitter and oxidative damage in the toxicity process of rat injury by methylmercury was...In order to study the molecular mechanism of injury in rat organs induced by methylmercury, and the relationship between neurotransmitter and oxidative damage in the toxicity process of rat injury by methylmercury was studied. The control group was physiological saline of 0.9%, the concentration of exposure groups were 5 mg/(kg5d) and 10 mg/(kg5d) respectively. The content of AChE, ACh, NOS, NO, MDA, SOD, GSH-Px and GSH in different organs of rats were determined with conventional methods. The results showed that after exposure to methylmercury for 7 d, the mercury content in brain of exposure groups increased clearly and had significant difference compared with the control group(P<0.01). In rat's brain, serum, liver and kidney, the content of ACh and AChE were all decreased; the content of NOS and NO were all increased; the content of MDA was increased compared with the control group, the exposure groups had significant difference (P<0.01); the content of SOD, GSH and GSH-Px was decreased compared with the control group, the exposure groups had significant difference(P<0.01). It could be concluded that methylmercury did effect the change of neurotransmitter and free radical. They participated in the toxicity process of injury by methylmercury. The damage of neurotransmitter maybe cause the chaos of free radical and the chaos of free radical may also do more damage to neurotransmitter vice versa.展开更多
Increasing evidence suggests that food ingested polyphenols can have beneficial effects in neuronal protection acting against oxidative stress and inflammatory injury. Moreover, polyphenols have been reported to promo...Increasing evidence suggests that food ingested polyphenols can have beneficial effects in neuronal protection acting against oxidative stress and inflammatory injury. Moreover, polyphenols have been reported to promote cognitive functions. Biotransformation of polyphenols is needed to obtain metabolites active in brain and it occurs through their processing by gut microbiota. Polyphenols metabolites could directly act as neurotransmitters crossing the blood-brain barrier or indirectly by modulating the cerebrovascular system. The microbiota-gut-brain axis is considered a neuroendocrine system that acts bidirectionally and plays an important role in stress responses. The metabolites produced by microbiota metabolism can modulate gut bacterial composition and brain biochemistry acting as neurotransmitters in the central nervous system. Gut microbiota composition can be influenced by dietary ingestion of natural bioactive molecules such as probiotics, prebiotics and polyphenol. Microbiota composition can be altered by dietary changes and gastrointestinal dysfunctions are observed in neurodegenerative diseases. In addition, several pieces of evidence support the idea that alterations in gut microbiota and enteric neuroimmune system could contribute to onset and progression of these age-related disorders. The impact of polyphenols on microbiota composition strengthens the idea that maintaining a healthy microbiome by modulating diet is essential for having a healthy brain across the lifespan. Moreover, it is emerging that they could be used as novel therapeutics to prevent brain from neurodegeneration.展开更多
The present study analyzed expressional changes of excitatory neurotransmitters and inhibitory neurotransmitters in the rat corpus striatum after single-use and combined-use diazepam and Chinese herb moschus. The infl...The present study analyzed expressional changes of excitatory neurotransmitters and inhibitory neurotransmitters in the rat corpus striatum after single-use and combined-use diazepam and Chinese herb moschus. The influence of moschus on the central nervous system was analyzed, in particular whether moschus increased penetration of other drugs into the brain. Reverse-phase high-performance liquid chromatography, which included pre-column derivation with orthophthaladehyde detection, showed varied increased levels of excitatory neurotransmitters, including aspartate and glutamate, and inhibitory neurotransmitters, including glycine and Y-aminobutyric acid, in the corpus striatum after treatment with moschus alone, diazepam alone, or a combination of both. Compared with the diazepam group, aspartate levels significantly decreased at 30 and 60-105 minutes after combined treatment with moschus, while glutamate significantly increased at 45 and 75-105 minutes, glycine levels significantly increased at 105 minutes, and γ-aminobutyric acid increased at 30 and 75-105 minutes. These findings suggested that moschus increased the inhibition effects of diazepam on the brain.展开更多
BACKGROUND: Encephalofluctuograph Technology (ET) is an advanced and non-traumatic analytical method of brain function. ET can acquire super-slow waves from electroencephalic signals. Studies have shown that these ...BACKGROUND: Encephalofluctuograph Technology (ET) is an advanced and non-traumatic analytical method of brain function. ET can acquire super-slow waves from electroencephalic signals. Studies have shown that these particular spectra can reflect neurochemical processes in the brain. OBJECTIVE: To verify neurotransmitter changes in the brains Parkinson's disease (PD) patients through the use of ET. DESIGN, TIME AND SETTING: A non-randomized concurrent control experiment was performed at the Department of Neurology in Southern Building, General Hospital of Chinese PLA from August to December 2007. PARTICIPANTS: Sixty-one outpatients with PD were selected from the General Hospital of Chinese PLA from August 2007 to December 2007. In addition, 48 healthy subjects were selected as normal controls. METHODS: All patients underwent assessment of the sub scale Ⅱ, Ⅲ and V of the Unified Parkinson's Disease Rating Scale (UPDRS), in which part Ⅱ was used to inform activity of daily living, part Ⅲ reflected athletic ability, and part Ⅴ was the Hoehn & Yahr grade for symptoms evaluation. Correlation analysis was performed between dopamine levels and UPDRS assessment. Neurotransmitter changes were observed forty-eight prior to and 1.5 hours after medicating with Benserazide. The S1, S2, S4, S5, S7, and S 11 spectras respectively reflect gamma-aminobutyric acid (GABA), glutamic acid (Glu), 5-hydroxytryptamine (5-HT), acetylcholine (ACh), norepinephrine, and dopamine. MAIN OUTCOME MEASURES: Neurotransmitter changes in the brains of all subjects, and correlations between dopamine concentrations and UPDRS assessment. Neurotransmitter changes in a subgroup of patients prior to and 1.5 hours after medicating with Benserazide. RESULTS: Concentrations of 5-HT, ACh, and norepinephrine were decreased in the PD group, and GABA was increased. However, there was no significant difference compared with the normal control group (P 〉 0.05). The level of dopamine in PD group was significantly lower than that in the control group (P 〈 0.01 ). Dopamine concentrations in PD patients negatively correlated with UPDRS scores and the Hoehn &Yahr grade range (r = 0.4601, -0.4301, P 〈 0.01). Dopamine levels increased significantly in PD patients 1.5 hours after medicating with Benserazide compared with before (P 〈 0.01). CONCLUSION: Detection by ET demonstrated that dopamine concentrations were significantly decreased in the brains of PD patients, as well as played a role in the course of pathogenesis and therapy. These results provided useful information for future non-traumatic of PD.展开更多
Spinal cord injury is linked to the interruption of neural pathways,which results in irreversible neural dysfunction.Neural repair and neuroregeneration are critical goals and issues for rehabilitation in spinal cord ...Spinal cord injury is linked to the interruption of neural pathways,which results in irreversible neural dysfunction.Neural repair and neuroregeneration are critical goals and issues for rehabilitation in spinal cord injury,which require neural stem cell repair and multimodal neuromodulation techniques involving personalized rehabilitation strategies.Besides the involvement of endogenous stem cells in neurogenesis and neural repair,exogenous neural stem cell transplantation is an emerging effective method for repairing and replacing damaged tissues in central nervous system diseases.However,to ensure that endogenous or exogenous neural stem cells truly participate in neural repair following spinal cord injury,appropriate interventional measures(e.g.,neuromodulation)should be adopted.Neuromodulation techniques,such as noninvasive magnetic stimulation and electrical stimulation,have been safely applied in many neuropsychiatric diseases.There is increasing evidence to suggest that neuromagnetic/electrical modulation promotes neuroregeneration and neural repair by affecting signaling in the nervous system;namely,by exciting,inhibiting,or regulating neuronal and neural network activities to improve motor function and motor learning following spinal cord injury.Several studies have indicated that fine motor skill rehabilitation training makes use of residual nerve fibers for collateral growth,encourages the formation of new synaptic connections to promote neural plasticity,and improves motor function recovery in patients with spinal cord injury.With the development of biomaterial technology and biomechanical engineering,several emerging treatments have been developed,such as robots,brain-computer interfaces,and nanomaterials.These treatments have the potential to help millions of patients suffering from motor dysfunction caused by spinal cord injury.However,large-scale clinical trials need to be conducted to validate their efficacy.This review evaluated the efficacy of neural stem cells and magnetic or electrical stimulation combined with rehabilitation training and intelligent therapies for spinal cord injury according to existing evidence,to build up a multimodal treatment strategy of spinal cord injury to enhance nerve repair and regeneration.展开更多
The present study collected cerebrospinal fluid samples from the corpus striatum in rats treated with borneol, moschus, storax, and acorus tatarinowii using brain microdialysis technology. Levels of excitatory neurotr...The present study collected cerebrospinal fluid samples from the corpus striatum in rats treated with borneol, moschus, storax, and acorus tatarinowii using brain microdialysis technology. Levels of excitatory neurotransmitters aspartic acid and glutamate, as well as inhibitory neurotransmitters glycine and ^-aminobutyric acid, were measured in samples using reversed-phase high-performance liquid chromatography, phosphate gradient elution, and fluorescence detection. Results showed that concentrations of all four amino acid neurotransmitters significantly increased in the corpus striatum following treatment with borneol or moschus, but effects due to borneol were more significant than moschus. Acorus tatarinowii treatment increased ^-aminobutyric acid expression, but decreased glutamate concentrations. Storax increased aspartic acid concentrations and decreased glycine expression. Results demonstrated that borneol and moschus exhibited significant effects on con amino acid neurotransmitter expression; storax exhibited excitatory effects and acorus tatarinowii resulted in inhibitory effects.展开更多
The neurotransmitter level changes of ducks exposed 8-month in a mercury-polluted site(Wanshan, China) and a reference site(Shanghai, China) were examined. Chemical analyses showed both higher mercury and selenium con...The neurotransmitter level changes of ducks exposed 8-month in a mercury-polluted site(Wanshan, China) and a reference site(Shanghai, China) were examined. Chemical analyses showed both higher mercury and selenium concentrations in the organ of Wanshan ducks. An increased content of acetylcholine(ACh) in brain and blood and a decreased activity of acetylcholinesterase(AChE) in blood were observed. Moreover, there was an increasing trend for nitric oxide synthase(NOS) activity and nitric oxide(NO) production in duck brain, but a reduction of NOS activity in duck serum. The possible explanations were due to the interactive effect of selenium accumulation and the sublethal exposure level of mercury in Wanshan area. The present study showed that AChE and NOS were sensitive to mercury contamination of real circumstance, suggesting that these two indexes have the potential to be biomarkers in assessment of health effects by mercury contamination.展开更多
Shuyusan, a traditional Chinese medicine, was shown to improve depression symptoms and behavioral scores, as well as increase 5-hydroxytryptamine (5-HT), 5-hydroxyindoleacetic acid, and 5-hydroxytryptophan levels, i...Shuyusan, a traditional Chinese medicine, was shown to improve depression symptoms and behavioral scores, as well as increase 5-hydroxytryptamine (5-HT), 5-hydroxyindoleacetic acid, and 5-hydroxytryptophan levels, in a rat model of chronic stress-induced depression. However, dopamine, noradrenalin, and 3-methoxy-4-hydroxyphenylglycol expressions remained unchanged following Shuyusan treatment. Compared with the model group, the number of 5-HT-positive neurons in layers 4-5 of the frontal cortex, as well as hippocampal CA1 and CA3 regions, significantly increased following Shuyusan treatment. These results suggested that Shuyusan improved symptoms in a rat model of chronic stress-induced depression with mechanisms that involved 5-HT, 5-HT metabolite, 5-HT precursor expressions.展开更多
The larvae of ascidian Styela canopus Savigny were treated with epinephrine, norepinephrine, L-DOPA, GABA and thyroxin to test the ability of these compounds to induce or inhibit larval settlement and metamorphosis. T...The larvae of ascidian Styela canopus Savigny were treated with epinephrine, norepinephrine, L-DOPA, GABA and thyroxin to test the ability of these compounds to induce or inhibit larval settlement and metamorphosis. The results showed that epinephrine, norepinephrine and L-DOPA at the concentration of 1 μmol/dm^3 induced larval settlement and metamorphosis in S. canopus, with short exposure ( 1 h) to 1 μmol/dm^3 of L-DOPA inducing rapid settlement. In contrast, GABA at the concentrations of 0.1 ~1130.0 μmol/dm^3 significantly inhibited the settlement and metamorphosis of S. canopus larvae. In addition, thyroxin at 1 -50 μg/dm^3 had no effect on larval settlement and metamorphosis in S. canopus. These results suggest the importance of neurotransmitters in the settlement and metamorphosis of S. canopus larvae.展开更多
The present study established a mouse model of depression induced by unpredictable chronic mild stress. The model mice were treated with Yulangsan polysaccharide (YLSPS; 150, 300 and 600 mg/kg) for 21 days, and comp...The present study established a mouse model of depression induced by unpredictable chronic mild stress. The model mice were treated with Yulangsan polysaccharide (YLSPS; 150, 300 and 600 mg/kg) for 21 days, and compared with fluoxetine-treated and normal control groups. Enzyme-linked immunosorbent assay, radioimmunity and immunohistochemical staining showed that following treatment with YLSPS (300 and 600 mg/kg), monoamine neurotransmitter levels, prefrontal cortex adenylate cyclase activity and hippocampal brain-derived neurotrophic factor expression were significantly elevated, and depression-like behaviors were improved. Open-field and novelty-suppressed feeding tests showed that mouse activity levels were increased and feeding latency was shortened following treatment. Our results indicate that YLSPS inhibits depression by upregulating monoamine neurotransmitters, prefrontal cortex adenylate cyclase activity and hippocampal brain-derived neurotrophic factor expression.展开更多
BACKGROUND: Changes in central neurotransmitter expression play an important role in stress response and forms the basis for stress-induced psychological and behavior changes. OBJECTIVE: To observe the effects of di...BACKGROUND: Changes in central neurotransmitter expression play an important role in stress response and forms the basis for stress-induced psychological and behavior changes. OBJECTIVE: To observe the effects of different restraint stress intervals on brain monoamine neurotransmitter expression, and to investigate the correlation between stress response and neurotransmitter levels. DESIGN: Randomized controlled animal study. SETTING: Chinese Herb and Natural Medicine Institute, Pharmacological College of Jinan University. MATERIALS: Sixty 7-week-old male Kunming mice of clean grade, weighing 18-22 g, were provided by the Guangdong Medical Experimental Animal Center. The experiment was in accordance with animal ethics standards. METHODS: This study was performed at the Chinese Herb and Natural Medicine Institute, Pharmacological College of Jinan University from June 2006 to May 2007. A restraint device for mice was constructed according to published reports. Experimental mice were adaptively fed for 1 week and randomly divided into a control group (n = 10) and an experimental group (n = 50). The experimental group was sub-divided into five restraint intervals: 4, 8, 12, 18, and 24 hours (n = 10 mice per time point). Animals in the experimental group were not allowed to eat or drink during the restraint period. Mice in the control group did not undergo restraint, but had identical food and water restrictions. Cerebral cortex and hypothalamus were separated based on observational times and protein was extracted using perchloric acid. Central monoamine neurotransmitter levels were measured using high performance liquid chromatography with electrochemical detection. MAIN OUTCOME MEASURES: Levels of norepinephrine (NE), dopamine hydrochloride (DA), 3,4-dihydroxyphen-ylanetic acid (DOPAC), homovanillic acid (HVA), 5-hydroxytryptamine (5-HT), and 5-hydroxyindoleac-etic acid (5-HIAA) in the cerebral cortex and hypothalamus of mice. RESULTS: Sixty mice were included in the final analysis. ① NE levels in the cerebral cortex, hypothalamus, and plasma: four hours after restraint, NE levels in the cerebral cortex and hypothalamus ere significantly lower than control levels (P 〈 0.05). After 12 hours of restraint, NE levels in the experimental group were significantly higher than in the control group (P 〈 0.05). At 18 hours of restraint, there was no significant difference in NE levels in the cerebral cortex between the experimental group and the control group (P 〉 0.05). In addition, NE levels in the plasma gradually increased with longer restraint time, which was significant between experimental groups and the control group (P 〈 0.05-0.01). ② Levels of DA, DOPAC, and HVA in the cerebral cortex and hypothalamus: there were significant differences in DA levels in the cerebral cortex and hypothalamus after 18 and 24 hours of restraint compared to control animals (P 〈 0.05). DOPAC and HVA levels in the cerebral cortex were enhanced with longer restraint time, and there was significant difference in all restraint groups compared to control levels (P 〈 0.01), except for DOPAC levels after 4 hours of restraint. Moreover, DOPAC and HVA levels in the hypothalamus were enhanced with increasing restraint time. Levels of 5-HT and 5-HIAA in the cerebral cortex and hypothalamus: after short restraint periods and in the control group, 5-HT was not detectable. However, it was quantitatively detected at 12 hours after restraint. The 5-HT levels in the cerebral cortex and hypothalamus reached peak levels at 12 and 18 hours of restraint. 5-HIAA levels in the cerebral cortex and hypothalamus showed a similar tendency to increase with restraint time- 5-HIAA levels at 4-8 hours after restraint were significantly higher than control levels (P 〈 0.01). The 5-HIAA levels decreased at 12 hours after restraint, but remained significantly higher than the control group (P 〈 0.05). CONCLUSION: Restraint stress affects the hypothalamic-pituitary-adrenal (HPA) axis and causes changes in monoamine neurotransmitters in brain tissues, which suggests stress status could be improved by adjusting HPA axis and neurotransmitter levels in the brain.展开更多
基金supported by the National Natural Science Foundation of China(81870841 and 82171192 to X.S.L.,82101349 to G.L.Q.)。
文摘General anesthesia is widely applied in clinical practice.However,the precise mechanism of loss of consciousness induced by general anesthetics remains unknown.Here,we measured the dynamics of five neurotransmitters,includingγ-aminobutyric acid,glutamate,norepinephrine,acetylcholine,and dopamine,in the medial prefrontal cortex and primary visual cortex of C57BL/6 mice through in vivo fiber photometry and genetically encoded neurotransmitter sensors under anesthesia to reveal the mechanism of general anesthesia from a neurotransmitter perspective.Results revealed that the concentrations of γ-aminobutyric acid,glutamate,norepinephrine,and acetylcholine increased in the cortex during propofol-induced loss of consciousness.Dopamine levels did not change following the hypnotic dose of propofol but increased significantly following surgical doses of propofol anesthesia.Notably,the concentrations of the five neurotransmitters generally decreased during sevoflurane-induced loss of consciousness.Furthermore,the neurotransmitter dynamic networks were not synchronized in the non-anesthesia groups but were highly synchronized in the anesthetic groups.These findings suggest that neurotransmitter dynamic network synchronization may cause anesthetic-induced loss of consciousness.
文摘Non-invasive cerebral neuromodulation technologies are essential for the reorganization of cerebral neural networks,which have been widely applied in the field of central neurological diseases,such as stroke,Parkinson’s disease,and mental disorders.Although significant advances have been made in neuromodulation technologies,the identification of optimal neurostimulation paramete rs including the co rtical target,duration,and inhibition or excitation pattern is still limited due to the lack of guidance for neural circuits.Moreove r,the neural mechanism unde rlying neuromodulation for improved behavioral performance remains poorly understood.Recently,advancements in neuroimaging have provided insight into neuromodulation techniques.Functional near-infrared spectroscopy,as a novel non-invasive optical brain imaging method,can detect brain activity by measuring cerebral hemodynamics with the advantages of portability,high motion tole rance,and anti-electromagnetic interference.Coupling functional near-infra red spectroscopy with neuromodulation technologies offe rs an opportunity to monitor the cortical response,provide realtime feedbac k,and establish a closed-loop strategy integrating evaluation,feedbac k,and intervention for neurostimulation,which provides a theoretical basis for development of individualized precise neuro rehabilitation.We aimed to summarize the advantages of functional near-infra red spectroscopy and provide an ove rview of the current research on functional near-infrared spectroscopy in transcranial magnetic stimulation,transcranial electrical stimulation,neurofeedback,and braincomputer interfaces.Furthermore,the future perspectives and directions for the application of functional near-infrared spectroscopy in neuromodulation are summarized.In conclusion,functional near-infrared spectroscopy combined with neuromodulation may promote the optimization of central pellral reorganization to achieve better functional recovery form central nervous system diseases.
基金supported by the National Natural Science Foundation of China,No.82071419Key Research and Development Program of Guangzhou,No.202206010086+1 种基金High-level Hospital Construction Project,No.DFJH201907Supporting Research Funds for Outstanding Young Medical Talents in Guangdong Province,No.KJ012019442(all to YZ)。
文摘The dichotomized brain system is a concept that was generalized from the‘dual syndrome hypothesis’to explain the heterogeneity of cognitive impairment,in which anterior and posterior brain systems are independent but partially overlap.The dopaminergic system acts on the anterior brain and is responsible for executive function,working memory,and planning.In contrast,the cholinergic system acts on the posterior brain and is responsible for semantic fluency and visuospatial function.Evidence from dopaminergic/cholinergic imaging or functional neuroimaging has shed significant insight relating to the involvement of the cerebellum in the cognitive process of patients with Parkinson’s disease.Previous research has reported evidence that the cerebellum receives both dopaminergic and cholinergic projections.However,whether these two neurotransmitter systems are associated with cognitive function has yet to be fully elucidated.Furthermore,the precise role of the cerebellum in patients with Parkinson’s disease and cognitive impairment remains unclear.Therefore,in this review,we summarize the cerebellar dopaminergic and cholinergic projections and their relationships with cognition,as reported by previous studies,and investigated the role of the cerebellum in patients with Parkinson’s disease and cognitive impairment,as determined by functional neuroimaging.Our findings will help us to understand the role of the cerebellum in the mechanisms underlying cognitive impairment in Parkinson’s disease.
基金Supported by the Academic Leaders Training Program of Pudong Health Bureau of Shanghai,No.PWRd2023-03Clinical Research Fund of Shanghai Municipal Commission of Health,No.202040136+1 种基金National Natural Science Foundation of China,No.82070842Jiangxi Health Commission Science and Technology Plan Project,No.202212838 and No.202212852.
文摘BACKGROUND Cognitive dysfunction is the main manifestation of central neuropathy.Although cognitive impairments tend to be overlooked in patients with diabetes mellitus(DM),there is a growing body of evidence linking DM to cognitive dysfunction.Hyperglycemia is closely related to neurological abnormalities,while often disregarded in clinical practice.Changes in cerebral neurotransmitter levels are associated with a variety of neurological abnormalities and may be closely related to blood glucose control in patients with type 2 DM(T2DM).AIM To evaluate the concentrations of cerebral neurotransmitters in T2DM patients exhibiting different hemoglobin A1c(HbA1c)levels.METHODS A total of 130 T2DM patients were enrolled at the Department of Endocrinology of Shanghai East Hospital.The participants were divided into four groups according to their HbA1c levels using the interquartile method,namely Q1(<7.875%),Q2(7.875%-9.050%),Q3(9.050%-11.200%)and Q4(≥11.200%).Clinical data were collected and measured,including age,height,weight,neck/waist/hip circumferences,blood pressure,comorbidities,duration of DM,and biochemical indicators.Meanwhile,neurotransmitters in the left hippocampus and left brainstem area were detected by proton magnetic resonance spectroscopy.RESULTS The HbA1c level was significantly associated with urinary microalbumin(mALB),triglyceride,low-density lipoprotein cholesterol(LDL-C),homeostasis model assessment of insulin resistance(HOMA-IR),and beta cell function(HOMA-β),N-acetylaspartate/creatine(NAA/Cr),and NAA/choline(NAA/Cho).Spearman correlation analysis showed that mALB,LDL-C,HOMA-IR and NAA/Cr in the left brainstem area were positively correlated with the level of HbA1c(P<0.05),whereas HOMA-βwas negatively correlated with the HbA1c level(P<0.05).Ordered multiple logistic regression analysis showed that NAA/Cho[Odds ratio(OR):1.608,95%confidence interval(95%CI):1.004-2.578,P<0.05],LDL-C(OR:1.627,95%CI:1.119-2.370,P<0.05),and HOMA-IR(OR:1.107,95%CI:1.031-1.188,P<0.01)were independent predictors of poor glycemic control.CONCLUSION The cerebral neurotransmitter concentrations in the left brainstem area in patients with T2DM are closely related to glycemic control,which may be the basis for the changes in cognitive function in diabetic patients.
文摘T cells are essential for a healthy life,performing continuously:immune surveillance,recognition,protection,activation,suppression,assistance,eradication,secretion,adhesion,migration,homing,communications,and additional tasks.This paper describes five aspects of normal beneficial T cells in the healthy or diseased brain.First,normal beneficial T cells are essential for normal healthy brain functions:cognition,spatial learning,memory,adult neurogenesis,and neuroprotection.T cells decrease secondary neuronal degeneration,increase neuronal survival after central nervous system(CNS) injury,and limit CNS inflammation and damage upon injury and infection.Second,while pathogenic T cells contribute to CNS disorders,recent studies,mostly in animal models,show that specific subpopulations of normal beneficial T cells have protective and regenerative effects in seve ral neuroinflammatory and neurodegenerative diseases.These include M ultiple Sclerosis(MS),Alzheimer’s disease,Parkinson’s disease,Amyotrophic Lateral Sclerosis(ALS),stro ke,CNS trauma,chronic pain,and others.Both T cell-secreted molecules and direct cell-cell contacts deliver T cell neuroprotective,neuro regenerative and immunomodulato ry effects.Third,normal beneficial T cells are abnormal,impaired,and dysfunctional in aging and multiple neurological diseases.Different T cell impairments are evident in aging,brain tumors(mainly Glioblastoma),seve re viral infections(including COVID-19),chro nic stress,major depression,schizophrenia,Parkinson’s disease,Alzheimer’s disease,ALS,MS,stro ke,and other neuro-pathologies.The main detrimental mechanisms that impair T cell function are activation-induced cell death,exhaustion,senescence,and impaired T cell stemness.Fo urth,several physiological neurotransmitters and neuro peptides induce by themselves multiple direct,potent,beneficial,and therapeutically-relevant effects on normal human T cells,via their receptors in T cells.This scientific field is called "Nerve-Driven Immunity".The main neurotransmitters and neuropeptides that induce directly activating and beneficial effects on naive normal human T cells are:dopamine,glutamate,GnRH-Ⅱ,neuropeptide Y,calcitonin gene-related peptide,and somatostatin.Fifth, "Personalized Adoptive Neuro-Immunotherapy".This is a novel unique cellular immunotherapy,based on the "Nerve-Driven Immunity" findings,which was recently designed and patented for safe and repeated rejuvenation,activation,and improvement of impaired and dysfunctional T cells of any person in need,by ex vivo exposure of the person’s T cells to neurotransmitters and neuropeptides.Personalized adoptive neuro-immunotherapy includes an early ex vivo personalized diagnosis,and subsequent ex vivo in vivo personalized adoptive therapy,tailo red according to the diagnosis.The Personalized Adoptive Neuro-Immunotherapy has not yet been tested in humans,pending validation of safety and efficacy in clinical trials,especially in brain tumors,chronic infectious diseases,and aging,in which T cells are exhausted and/or senescent and dysfunctional.
文摘Alzheimer’s disease(AD)is a neurodegenerative condition that disrupts nerve cell function due to the misfolding and buildup of proteins,resulting in cognitive loss and aberrant behavior.Microglia cellsare one of the crucial immune cells in the central nervous system.Depending on their activation levels,microglia cells in the degenerative phase of AD can serve either neuroprotective or neurotoxic roles.Microglia cells express several neurotransmitter receptors that play distinct functions in the degenerative progression of AD.These receptors facilitate bidirectional communication between microglia and nerve cells.The neurotransmitter receptors on microglia cells can mediate or affect the neuroprotective or toxic effects of microglia cells,thereby affecting AD pathology.This paper focuses on the gamma-aminobutyric acid,glutaminergic,cannabinoid,cholinergic,and adrenergic receptors on microglia cells and their relationship with AD.Understanding how neurotransmitter receptors on microglia function in AD will be crucial for identifying potential treatment targets.
文摘BACKGROUND In patients with schizophrenia,the brain structure and neurotransmitter levels change,which may be related to the occurrence and progression of this disease.AIM To explore the relationships between changes in neurotransmitters,brain structural characteristics,and the scores of the Positive and Negative Symptom Scale(PANSS)in patients with first-episode schizophrenia.METHODS The case group comprised 97 patients with schizophrenia,who were evaluated using the Canadian Neurological Scale and confirmed by laboratory tests at Ningbo Mental Hospital from January 2020 to July 2022.The control group comprised 100 healthy participants.For all participants,brain structural characteristics were explored by measuring brain dopamine(DA),glutamic acid(Glu),and gamma-aminobutyric acid(GABA)levels,with magnetic resonance imaging.The case group was divided into negative and positive symptom subgroups using PANSS scores for hierarchical analysis.Linear correlation analysis was used to analyze the correlations between neurotransmitters,brain structural character istics,and PANSS scores.RESULTS Patients in the case group had higher levels of DA and lower levels of Glu and GABA,greater vertical and horizontal distances between the corpus callosum and the inferior part of the fornix and larger ventricle area than patients in the control group(P<0.05).Patients with positive schizophrenia symptoms had significantly higher levels of DA,Glu,and GABA than those with negative symptoms(P<0.05).In patients with positive schizophrenia symptoms,PANSS score was significantly positively correlated with DA,vertical and horizontal distances between the corpus callosum and the infrafornix,and ventricular area,and was significantly negatively correlated with Glu and GABA(P<0.05).In patients with negative schizophrenia symptoms,PANSS score was significantly positively correlated with DA,vertical distance between the corpus callosum and the infrafornix,horizontal distance between the corpus callosum and the infrafornix,and ventricular area,and was significantly negatively correlated with Glu and GABA(P<0.05).CONCLUSION In patients with first-episode schizophrenia,DA levels increased,Glu and GABA levels decreased,the thickness of the corpus callosum increased,and these variables were correlated with PANSS scores.
基金Supported by The Natural Science Foundation of Guizhou Province (Qiankehe Jichu[2020]1Y362)Special Project for Scientific and Technological Research on Traditional Chinese Medicine and Ethnic Medicine of Guizhou Province(QZYY-2021-016)+1 种基金The Natural Science Foundation of Guizhou Province(Qiankehe Jichu-ZK[2022]Yiban 510)Young Science and Technology Talents Growth Project of Guizhou Provincial Department of Education (Qian Jiao He KY Zi[2022]No. 261)。
文摘[Objectives] This study was carried out to explore the combined effects of Fu Zi(Radix Aconiti Lateralis Praeparata, the secondary root of perennial herbaceous plant Acontium carmichaeli Dehx. of family Ranunculaceae) and Rou Gui(Cortex Cinnamomi, the bark of Cinnamamunz cassia Presl of family Lauraceae) on intestinal neurotransmitters and microflora in rats with slow transit constipation(STC). [Methods] Experimental rats were given loperamide hydrochloride by gavage to induce STC, and then treated with Fu Zi alone, Rou Gui alone, a combination of Fu Zi and Rou Gui(2:1 w/w), and prucalopride, respectively, for 14 days. Meanwhile, the general condition, the time to first black stool and the rate of intestinal propulsion of rats in each group were observed after STC was induced and after drug treatment, and the pathological changes in rat colon were observed via hematoxylin-eosin(HE) staining, and the levels of colonic 5-hydroxytryptamine(HT), vasoactive intestinal peptide(VIP) and substance P(SP) were detected by ELISA, and the changes in intestinal flora were detected by 16S rRNA Real-time PCR. [Results] Compared with healthy rats, the time to first black stool and the rate of intestinal propulsion, colonic 5-HT and SP levels significantly decreased(p<0.01), while their colonic VIP level significantly increased(p<0.01). Compared with STC rats, the time to first black stool, the rate of intestinal propulsion, colonic 5-HT and SP levels in Fu Zi-Rou Gui(2:1) treated rats and prucalopride treated rats significantly increased(p<0.01), while their colonic VIP level significantly decreased(p<0.01). There was no significant difference in alpha diversity between healthy rats and STC rats. However, analysis on beta diversity revealed that there were differences in microflora structure and composition between them. Compared with healthy rats, the relative abundance of Firmicutes and Proteobacteria in STC rats significantly increased, while that of Bacteroidetes decreased. Compared with STC rats, the relative abundance of Proteobacteria decreased and that of Bacteroidetes and Firmicutes increased in Fu Zi-Rou Gui(2:1) treated rats;the relative abundance of Bacteroidetes and Proteobacteria decreased while that of Firmicutes increased in Fu Zi treated rats;the relative abundance of Proteobacteria decreased while that of Bacteroidetes increased in Rou Gui treated rats;the relative abundance of Firmicutes and Proteobacteria decreased while that of Bacteroidetes increased in prucalopride treated rats. The intestinal flora in rats of all groups was dominated by Lactobacillus spp. and other genera of anaerobic bacteria. Compared with healthy rats, the relative abundance of Lactobacillus spp. and Clostridium spp. in STC rats decreased, while those of Blautia spp. and Ruminococcus spp. and Allobaculum spp. increased. Compared with STC rats, the relative abundance of Lactobacillus spp. in all rats treated with drugs increased. [Conclusions] The combination of Fu Zi and Rou Gui(2:1) can effectively improve intestinal motility in STC rats by regulating intestinal microbial community and the levels of colonic neurotransmitters.
文摘Acarbose is used to control postpran-dial blood glucose in patients with type 2 diabetes and impaired glucose tolerance,since it improves insulin re-sistance and reduces blood lipids and cardiovascular com-plications.However,in recent years,many studies have found that acarbose can mediate and regulate a variety of neurotransmitter-related diseases,although the mech-anisms are not clear.Therefore,this paper analyzes the clinical effect of acarbose and its mediating effect on neu-rotransmitters of mental disorders through insulin,brain-gut axis,and calorie restriction,to provide a reference for the new clinical applications of acarbose.
基金The National Natural Science Foundation of China(No. 20177013) and the Younger Research of Shanghai Jiaotong University
文摘In order to study the molecular mechanism of injury in rat organs induced by methylmercury, and the relationship between neurotransmitter and oxidative damage in the toxicity process of rat injury by methylmercury was studied. The control group was physiological saline of 0.9%, the concentration of exposure groups were 5 mg/(kg5d) and 10 mg/(kg5d) respectively. The content of AChE, ACh, NOS, NO, MDA, SOD, GSH-Px and GSH in different organs of rats were determined with conventional methods. The results showed that after exposure to methylmercury for 7 d, the mercury content in brain of exposure groups increased clearly and had significant difference compared with the control group(P<0.01). In rat's brain, serum, liver and kidney, the content of ACh and AChE were all decreased; the content of NOS and NO were all increased; the content of MDA was increased compared with the control group, the exposure groups had significant difference (P<0.01); the content of SOD, GSH and GSH-Px was decreased compared with the control group, the exposure groups had significant difference(P<0.01). It could be concluded that methylmercury did effect the change of neurotransmitter and free radical. They participated in the toxicity process of injury by methylmercury. The damage of neurotransmitter maybe cause the chaos of free radical and the chaos of free radical may also do more damage to neurotransmitter vice versa.
基金supported by Italian Ministry of Health ‘‘Ricerca Corrente”(to SF)
文摘Increasing evidence suggests that food ingested polyphenols can have beneficial effects in neuronal protection acting against oxidative stress and inflammatory injury. Moreover, polyphenols have been reported to promote cognitive functions. Biotransformation of polyphenols is needed to obtain metabolites active in brain and it occurs through their processing by gut microbiota. Polyphenols metabolites could directly act as neurotransmitters crossing the blood-brain barrier or indirectly by modulating the cerebrovascular system. The microbiota-gut-brain axis is considered a neuroendocrine system that acts bidirectionally and plays an important role in stress responses. The metabolites produced by microbiota metabolism can modulate gut bacterial composition and brain biochemistry acting as neurotransmitters in the central nervous system. Gut microbiota composition can be influenced by dietary ingestion of natural bioactive molecules such as probiotics, prebiotics and polyphenol. Microbiota composition can be altered by dietary changes and gastrointestinal dysfunctions are observed in neurodegenerative diseases. In addition, several pieces of evidence support the idea that alterations in gut microbiota and enteric neuroimmune system could contribute to onset and progression of these age-related disorders. The impact of polyphenols on microbiota composition strengthens the idea that maintaining a healthy microbiome by modulating diet is essential for having a healthy brain across the lifespan. Moreover, it is emerging that they could be used as novel therapeutics to prevent brain from neurodegeneration.
文摘The present study analyzed expressional changes of excitatory neurotransmitters and inhibitory neurotransmitters in the rat corpus striatum after single-use and combined-use diazepam and Chinese herb moschus. The influence of moschus on the central nervous system was analyzed, in particular whether moschus increased penetration of other drugs into the brain. Reverse-phase high-performance liquid chromatography, which included pre-column derivation with orthophthaladehyde detection, showed varied increased levels of excitatory neurotransmitters, including aspartate and glutamate, and inhibitory neurotransmitters, including glycine and Y-aminobutyric acid, in the corpus striatum after treatment with moschus alone, diazepam alone, or a combination of both. Compared with the diazepam group, aspartate levels significantly decreased at 30 and 60-105 minutes after combined treatment with moschus, while glutamate significantly increased at 45 and 75-105 minutes, glycine levels significantly increased at 105 minutes, and γ-aminobutyric acid increased at 30 and 75-105 minutes. These findings suggested that moschus increased the inhibition effects of diazepam on the brain.
文摘BACKGROUND: Encephalofluctuograph Technology (ET) is an advanced and non-traumatic analytical method of brain function. ET can acquire super-slow waves from electroencephalic signals. Studies have shown that these particular spectra can reflect neurochemical processes in the brain. OBJECTIVE: To verify neurotransmitter changes in the brains Parkinson's disease (PD) patients through the use of ET. DESIGN, TIME AND SETTING: A non-randomized concurrent control experiment was performed at the Department of Neurology in Southern Building, General Hospital of Chinese PLA from August to December 2007. PARTICIPANTS: Sixty-one outpatients with PD were selected from the General Hospital of Chinese PLA from August 2007 to December 2007. In addition, 48 healthy subjects were selected as normal controls. METHODS: All patients underwent assessment of the sub scale Ⅱ, Ⅲ and V of the Unified Parkinson's Disease Rating Scale (UPDRS), in which part Ⅱ was used to inform activity of daily living, part Ⅲ reflected athletic ability, and part Ⅴ was the Hoehn & Yahr grade for symptoms evaluation. Correlation analysis was performed between dopamine levels and UPDRS assessment. Neurotransmitter changes were observed forty-eight prior to and 1.5 hours after medicating with Benserazide. The S1, S2, S4, S5, S7, and S 11 spectras respectively reflect gamma-aminobutyric acid (GABA), glutamic acid (Glu), 5-hydroxytryptamine (5-HT), acetylcholine (ACh), norepinephrine, and dopamine. MAIN OUTCOME MEASURES: Neurotransmitter changes in the brains of all subjects, and correlations between dopamine concentrations and UPDRS assessment. Neurotransmitter changes in a subgroup of patients prior to and 1.5 hours after medicating with Benserazide. RESULTS: Concentrations of 5-HT, ACh, and norepinephrine were decreased in the PD group, and GABA was increased. However, there was no significant difference compared with the normal control group (P 〉 0.05). The level of dopamine in PD group was significantly lower than that in the control group (P 〈 0.01 ). Dopamine concentrations in PD patients negatively correlated with UPDRS scores and the Hoehn &Yahr grade range (r = 0.4601, -0.4301, P 〈 0.01). Dopamine levels increased significantly in PD patients 1.5 hours after medicating with Benserazide compared with before (P 〈 0.01). CONCLUSION: Detection by ET demonstrated that dopamine concentrations were significantly decreased in the brains of PD patients, as well as played a role in the course of pathogenesis and therapy. These results provided useful information for future non-traumatic of PD.
基金supported by the Major International(Regional)Joint Research Project of the National Natural Science Foundation of China,No.81820108013(to LMC)the General Research Project of the National Natural Science Foundation of China,No.81772453(to DSX)the National Key Research and Development Program of China,No.2016YFA0100800(to LMC)
文摘Spinal cord injury is linked to the interruption of neural pathways,which results in irreversible neural dysfunction.Neural repair and neuroregeneration are critical goals and issues for rehabilitation in spinal cord injury,which require neural stem cell repair and multimodal neuromodulation techniques involving personalized rehabilitation strategies.Besides the involvement of endogenous stem cells in neurogenesis and neural repair,exogenous neural stem cell transplantation is an emerging effective method for repairing and replacing damaged tissues in central nervous system diseases.However,to ensure that endogenous or exogenous neural stem cells truly participate in neural repair following spinal cord injury,appropriate interventional measures(e.g.,neuromodulation)should be adopted.Neuromodulation techniques,such as noninvasive magnetic stimulation and electrical stimulation,have been safely applied in many neuropsychiatric diseases.There is increasing evidence to suggest that neuromagnetic/electrical modulation promotes neuroregeneration and neural repair by affecting signaling in the nervous system;namely,by exciting,inhibiting,or regulating neuronal and neural network activities to improve motor function and motor learning following spinal cord injury.Several studies have indicated that fine motor skill rehabilitation training makes use of residual nerve fibers for collateral growth,encourages the formation of new synaptic connections to promote neural plasticity,and improves motor function recovery in patients with spinal cord injury.With the development of biomaterial technology and biomechanical engineering,several emerging treatments have been developed,such as robots,brain-computer interfaces,and nanomaterials.These treatments have the potential to help millions of patients suffering from motor dysfunction caused by spinal cord injury.However,large-scale clinical trials need to be conducted to validate their efficacy.This review evaluated the efficacy of neural stem cells and magnetic or electrical stimulation combined with rehabilitation training and intelligent therapies for spinal cord injury according to existing evidence,to build up a multimodal treatment strategy of spinal cord injury to enhance nerve repair and regeneration.
基金supported by the National Natural Science Foundation of China, No. 81173572
文摘The present study collected cerebrospinal fluid samples from the corpus striatum in rats treated with borneol, moschus, storax, and acorus tatarinowii using brain microdialysis technology. Levels of excitatory neurotransmitters aspartic acid and glutamate, as well as inhibitory neurotransmitters glycine and ^-aminobutyric acid, were measured in samples using reversed-phase high-performance liquid chromatography, phosphate gradient elution, and fluorescence detection. Results showed that concentrations of all four amino acid neurotransmitters significantly increased in the corpus striatum following treatment with borneol or moschus, but effects due to borneol were more significant than moschus. Acorus tatarinowii treatment increased ^-aminobutyric acid expression, but decreased glutamate concentrations. Storax increased aspartic acid concentrations and decreased glycine expression. Results demonstrated that borneol and moschus exhibited significant effects on con amino acid neurotransmitter expression; storax exhibited excitatory effects and acorus tatarinowii resulted in inhibitory effects.
文摘The neurotransmitter level changes of ducks exposed 8-month in a mercury-polluted site(Wanshan, China) and a reference site(Shanghai, China) were examined. Chemical analyses showed both higher mercury and selenium concentrations in the organ of Wanshan ducks. An increased content of acetylcholine(ACh) in brain and blood and a decreased activity of acetylcholinesterase(AChE) in blood were observed. Moreover, there was an increasing trend for nitric oxide synthase(NOS) activity and nitric oxide(NO) production in duck brain, but a reduction of NOS activity in duck serum. The possible explanations were due to the interactive effect of selenium accumulation and the sublethal exposure level of mercury in Wanshan area. The present study showed that AChE and NOS were sensitive to mercury contamination of real circumstance, suggesting that these two indexes have the potential to be biomarkers in assessment of health effects by mercury contamination.
基金a grant from Science and Technology Bureau of Beijing, No.Z090507017709030
文摘Shuyusan, a traditional Chinese medicine, was shown to improve depression symptoms and behavioral scores, as well as increase 5-hydroxytryptamine (5-HT), 5-hydroxyindoleacetic acid, and 5-hydroxytryptophan levels, in a rat model of chronic stress-induced depression. However, dopamine, noradrenalin, and 3-methoxy-4-hydroxyphenylglycol expressions remained unchanged following Shuyusan treatment. Compared with the model group, the number of 5-HT-positive neurons in layers 4-5 of the frontal cortex, as well as hippocampal CA1 and CA3 regions, significantly increased following Shuyusan treatment. These results suggested that Shuyusan improved symptoms in a rat model of chronic stress-induced depression with mechanisms that involved 5-HT, 5-HT metabolite, 5-HT precursor expressions.
基金This research was supported by the National Natural Science Foundation of China under contract Nos 40276041 and 49976034.
文摘The larvae of ascidian Styela canopus Savigny were treated with epinephrine, norepinephrine, L-DOPA, GABA and thyroxin to test the ability of these compounds to induce or inhibit larval settlement and metamorphosis. The results showed that epinephrine, norepinephrine and L-DOPA at the concentration of 1 μmol/dm^3 induced larval settlement and metamorphosis in S. canopus, with short exposure ( 1 h) to 1 μmol/dm^3 of L-DOPA inducing rapid settlement. In contrast, GABA at the concentrations of 0.1 ~1130.0 μmol/dm^3 significantly inhibited the settlement and metamorphosis of S. canopus larvae. In addition, thyroxin at 1 -50 μg/dm^3 had no effect on larval settlement and metamorphosis in S. canopus. These results suggest the importance of neurotransmitters in the settlement and metamorphosis of S. canopus larvae.
基金supported by the Scientific Research and Technology Development Program of Guangxi Zhuang Autonomous Region, No. 0630002-2Athe National Natural Science Foundation of China, No. 30960504
文摘The present study established a mouse model of depression induced by unpredictable chronic mild stress. The model mice were treated with Yulangsan polysaccharide (YLSPS; 150, 300 and 600 mg/kg) for 21 days, and compared with fluoxetine-treated and normal control groups. Enzyme-linked immunosorbent assay, radioimmunity and immunohistochemical staining showed that following treatment with YLSPS (300 and 600 mg/kg), monoamine neurotransmitter levels, prefrontal cortex adenylate cyclase activity and hippocampal brain-derived neurotrophic factor expression were significantly elevated, and depression-like behaviors were improved. Open-field and novelty-suppressed feeding tests showed that mouse activity levels were increased and feeding latency was shortened following treatment. Our results indicate that YLSPS inhibits depression by upregulating monoamine neurotransmitters, prefrontal cortex adenylate cyclase activity and hippocampal brain-derived neurotrophic factor expression.
基金the National Key Technologies R&D Program, No: 2006BAIO6A20-09
文摘BACKGROUND: Changes in central neurotransmitter expression play an important role in stress response and forms the basis for stress-induced psychological and behavior changes. OBJECTIVE: To observe the effects of different restraint stress intervals on brain monoamine neurotransmitter expression, and to investigate the correlation between stress response and neurotransmitter levels. DESIGN: Randomized controlled animal study. SETTING: Chinese Herb and Natural Medicine Institute, Pharmacological College of Jinan University. MATERIALS: Sixty 7-week-old male Kunming mice of clean grade, weighing 18-22 g, were provided by the Guangdong Medical Experimental Animal Center. The experiment was in accordance with animal ethics standards. METHODS: This study was performed at the Chinese Herb and Natural Medicine Institute, Pharmacological College of Jinan University from June 2006 to May 2007. A restraint device for mice was constructed according to published reports. Experimental mice were adaptively fed for 1 week and randomly divided into a control group (n = 10) and an experimental group (n = 50). The experimental group was sub-divided into five restraint intervals: 4, 8, 12, 18, and 24 hours (n = 10 mice per time point). Animals in the experimental group were not allowed to eat or drink during the restraint period. Mice in the control group did not undergo restraint, but had identical food and water restrictions. Cerebral cortex and hypothalamus were separated based on observational times and protein was extracted using perchloric acid. Central monoamine neurotransmitter levels were measured using high performance liquid chromatography with electrochemical detection. MAIN OUTCOME MEASURES: Levels of norepinephrine (NE), dopamine hydrochloride (DA), 3,4-dihydroxyphen-ylanetic acid (DOPAC), homovanillic acid (HVA), 5-hydroxytryptamine (5-HT), and 5-hydroxyindoleac-etic acid (5-HIAA) in the cerebral cortex and hypothalamus of mice. RESULTS: Sixty mice were included in the final analysis. ① NE levels in the cerebral cortex, hypothalamus, and plasma: four hours after restraint, NE levels in the cerebral cortex and hypothalamus ere significantly lower than control levels (P 〈 0.05). After 12 hours of restraint, NE levels in the experimental group were significantly higher than in the control group (P 〈 0.05). At 18 hours of restraint, there was no significant difference in NE levels in the cerebral cortex between the experimental group and the control group (P 〉 0.05). In addition, NE levels in the plasma gradually increased with longer restraint time, which was significant between experimental groups and the control group (P 〈 0.05-0.01). ② Levels of DA, DOPAC, and HVA in the cerebral cortex and hypothalamus: there were significant differences in DA levels in the cerebral cortex and hypothalamus after 18 and 24 hours of restraint compared to control animals (P 〈 0.05). DOPAC and HVA levels in the cerebral cortex were enhanced with longer restraint time, and there was significant difference in all restraint groups compared to control levels (P 〈 0.01), except for DOPAC levels after 4 hours of restraint. Moreover, DOPAC and HVA levels in the hypothalamus were enhanced with increasing restraint time. Levels of 5-HT and 5-HIAA in the cerebral cortex and hypothalamus: after short restraint periods and in the control group, 5-HT was not detectable. However, it was quantitatively detected at 12 hours after restraint. The 5-HT levels in the cerebral cortex and hypothalamus reached peak levels at 12 and 18 hours of restraint. 5-HIAA levels in the cerebral cortex and hypothalamus showed a similar tendency to increase with restraint time- 5-HIAA levels at 4-8 hours after restraint were significantly higher than control levels (P 〈 0.01). The 5-HIAA levels decreased at 12 hours after restraint, but remained significantly higher than the control group (P 〈 0.05). CONCLUSION: Restraint stress affects the hypothalamic-pituitary-adrenal (HPA) axis and causes changes in monoamine neurotransmitters in brain tissues, which suggests stress status could be improved by adjusting HPA axis and neurotransmitter levels in the brain.