A review of the neurotransmitter system associated with cognitive function of the cerebellum in Parkinson's disease

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.

In vivo imaging reveals a synchronized correlation among neurotransmitter dynamics during propofol and sevoflurane anesthesia

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.

Correlation between cerebral neurotransmitters levels by proton magnetic resonance spectroscopy and HbA1c in patients with type 2 diabetes

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.

Effect of single-use versus combined-use moschus and diazepam on expression of amino acid neurotransmitters in the rat corpus striatum

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.

Effect of methylmercury on some neurotransmitters and oxidative damage of rats

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.

Effect of borneol, moschus, storax, and acorus tatarinowii on expression levels of four amino acid neurotransmitters in the rat corpus striatum

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.

Neuro faces of beneficial T cells:essential in brain,impaired in aging and neurological diseases,and activated functionally by neurotransmitters and neuropeptides

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.

Neurotransmitter changes in patients with Parkinson’s disease detected by encephalofluctuography technology: A non-randomized control study

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.

Neurotransmitter level changes in domestic ducks(Shaoxing duck) growing up in typical mercury contaminated area in China

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.

Effects of Shuyusan on monoamine neurotransmitters expression in a rat model of chronic stress-induced depression

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.

Effects of Yulangsan polysaccharide on monoamine neurotransmitters, adenylate cyclase activity and brain-derived neurotrophic factor expression in a mouse model of depression induced by unpredictable chronic mild stress

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.

Evolution of neurotransmitter gamma-aminobutyric acid,glutamate and their receptors

Gamma-aminobutyric acid(GABA)and glutamate are two important amino acid neurotransmitters widely present in the nervous systems of mammals,insects,round worm,and platyhelminths,while their receptors are quite diversified across different animal phyla.However,the evolutionary mechanisms between the two conserved neurotransmitters and their diversified receptors remain elusive,and antagonistic interactions between GABA and glutamate signal transduction systems,in particular,have begun to attract significant attention.In this review,we summarize the extant results on the origin and evolution of GABA and glutamate,as well as their receptors,and analyze possible evolutionary processes and phylogenetic relationships of various GABAs and glutamate receptors.We further discuss the evolutionary history of Excitatory/Neutral Amino Acid Transporter(EAAT),a transport protein,which plays an important role in the GABA-glutamate“yin and yang”balanced regulation.Finally,based on current advances,we propose several potential directions of future research.

Settlement and metamorphosis of Styela canopus Savigny larvae in response to some neurotransmitters and thyroxin

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.

Neurotransmitter regulation of extracellular signal-regulated kinase expression following subarachnoid hemorrhage

BACKGROUND： Very few studies have addressed neuronal injury in cerebral vasospasm and subarachnoid hemorrhage （SAH）, and the role of neurotransmitters in the regulation of extracellular signal-regulated kinase 1/2 （ERK1/2） expression following SAH. OBJECTIVE： To analyze neurotransmitter regulation of ERK1/2 expression through the use of signal transduction, and to investigate cerebral injury mechanisms following SAH. DESIGN, TIME AND SETTING： A completely randomized grouping and controlled animal experiment was performed at the Experimental Center of Medical College of Xi＇an Jiaotong University from March to December 2008. MATERIALS： Extraceliular signal-regulated ERK1/2 polyclonal antibody and streptavidin-peroxidase method kits were purchased from Beijing Biosynthesis Biotechnology, China; DAB kit was purchased from Zhongshan Golden Bridge Biotechnology, China; TUNEL kit was purchased from Promega, USA. METHODS： A total of 114 male, Sprague Dawley rats, aged 55-63 days old, were randomly assigned to five groups： SAH （n = 30）, saline control （n = 30）, puncture control （n = 30）, normal control （n = 6）, and neurotransmitter-treated （n = 18）. The SAH model was established by twice injecting blood through the cisterna magna. The neurotransmitters-treated group was subdivided into three groups according to drugs injected into the lateral cerebral ventricle： acetylcholine chloride, norepinephrine, and saline, with six animals in each group. MAIN OUTCOME MEASURES： Rats from the SAH, saline control, and puncture control groups were respectively sacrificed at 6, 12, and 24 hours, as well as 3 and 5 days, with six rats at each time point. The normal control group rats were sacrificed at 6 hours, and the neurotransmitter group rats were sacrificed 3 days following neurotransmitter injection. Morphological cellular changes were observed by hematoxylin and eosin staining. Immunohistochemical SP method was used to detect expression of ERK1/2 in the cortex, and cortical apoptosis was detected using the TUNEL method. RESULTS： Neural tissue edema, apoptosis, and necrosis occurred in the cortex of the SAH group. ERK1/2-positive cells were first observed at 6 hours, peaked at 12 hours following SAH in the cortex, and gradually decreased thereafter. Cellular apoptosis was observed in the cortex at 6 hours and peaked at 24 hours following SAH. ERK1/2 distribution in the brain overlapped apoptotic cells to a great degree. The number of ERK1/2-positive and apoptotic cells was significantly greater in the SAH group compared with the three control groups （P 〈 0.05）. Compared to the number of ERK1/2-positive cells in the saline-treated group, acetylcholine chloride treatment resulted in decreased ERK1/2 expression and apoptosis （P 〈 0.05）. Norepinephrine resulted in increased ERK1/2 expression, but there was no significance in apoptosis compared to the saline-treated group （P 〉 0.05）. CONCLUSION： Apoptosis was observed early in the rat cortex following SAH. In addition, ERK1/2 was expressed earlier than apoptosis. Acetylcholine chloride treatment resulted in decreased numbers of apoptotic cells following SAH, possibly by down-regulating ERK1/2 expression.

Influence of mesenteric lymph reperfusion on neurotransmitter expression in brain tissue of a superior mesenteric artery occlusion shock rat model

BACKGROUND： Previous studies have shown that mesenteric lymph reperfusion （MLR） exacerbates brain injury in a rat model of superior mesenteric artery occlusion （SMAO） shock. However, little is known about the influence of MLR on neurotransmitter expression in brain tissue. OBJECTIVE： To observe the effect of MLR on brain tissue injury by measuring monoamine and cholinergic neurotransmitter levels. DESIGN, TIME AND SETTING： A randomized, controlled, animal experiment was performed at the Institute of Microcirculation, Hebei North University, China; Research Room of Microcirculation and Laboratory of Biochemistry, Department of Pathophysiology, Basic Medical College, Hebei North University between December 2007 and March 2009. MATERIALS： Choline acetyltransferase （CHAT） and acetylcholine esterase （ACHE） kits were provided by Nanjing Jiancheng Bioengineering Institute, China; dopamine （DA） and noradrenalin （NE） standards were provided by the National Institute for the Control of Pharmaceutical and Biological Products; HP1100 chromatograph of liquid was provided by Agllent, USA. METHODS： A total of 24 male, Wistar rats were randomly assigned to 4 groups： sham-surgery, MLR SMAO, and MLR ＋ SMAO groups, with 6 rats in each group. In the MLR or SMAO groups, the mesenteric lymph duct or superior mesenteric artery was blocked for 1 hour. In the MLR ＋ SMAO group, the mesenteric lymph duct and superior mesenteric artery were occluded for 1 hour, followed by 2-hour repeffusion. ChAT and AChE levels were measured using the synthesized and hydrolyzed acetylcholine method, respectively. Liquid chromatography was employed to quantitatively analyze DA and NE levels, using relative retention time and the external standard method. MAIN OUTCOME MEASURES： CHAT, ACHE, DA, and NE levels. RESULTS： AChE levels were significantly increased, but ChAT levels were significantly decreased in the MLR and MLR ＋ SMAO groups following 2-hour repeffusion （P〈 0.01）. However, AChE activity in the MLR ＋ SMAO group was greater than in the MLR group （P 〈 0.05）. DA and NE levels were significantly decreased in the SMAO and MLR ＋ SMAO groups （P〈 0.01）, while DA levels in the MLR ＋ SMAO group were less than in the SMAO group （P 〈 0.05）. CONCLUSION： MLR exacerbated brain injury in a rat model of SMAO shock, which correlated with the intestinal lymphatic pathway. MLR decreased DA levels, but increased AChE activity, in a rat model of SMAO shock.

Effect of Schisandra chinensis polysaccharide on intracerebral acetylcholinesterase and monoamine neurotransmitters in a D-galactose-induced aging brain mouse model

BACKGROUND： The most prominent characteristic of brain aging is decreased learning and memory ability. The functions of learning and memory are closely related to intracerebral acetylcholinesterase （ACHE） and monoamine neurotransmitter activity. Previous studies have shown that Schisandra chinensis polysaccharide has an anti-aging effect. OBJECTIVE： To explore the effects of Schisandra chinensis polysaccharide on AChE activity and monoamine neurotransmitter content, as well as learning and memory ability in a D-galactose-induced aging mouse brain model compared with the positive control drug Kangnaoling. DESIGN, TIME AND SETTING： Completely randomized, controlled experiment based on neurobiochemistry was performed at the Pharmacological Laboratory, Henan University of Traditional Chinese Medicine from September to December 2003. MATERIALS： Schisandra chinensis was purchased from Henan Provincial Medicinal Company. Schisandra chinensis polysaccharide was obtained by water extraction and alcohol precipitation. Kangnaoling pellets were provided by Liaoning Tianlong Pharmaceutical （batch No. 20030804; state drug permit No. H21023095）. A total of 50 six-week-old Kunming mice were randomly divided into five groups： blank control, model, Kangnaoling, high and low dosage Schisandra chinensis polysaccharide groups, with 10 mice per group. METHODS： Mice in the blank control group were subcutaneously injected with 0.5 mL/20 g normal saline into the nape of the neck each day, while the remaining mice were subcutaneously injected with 5% D-galactose saline solution （0.5 mL/20 g） in the nape for 40 days to induce a brain aging model. On day 11, mice in the high and low dosage Schisandra chinensis polysaccharide groups were intragastrically infused with 20 mg/mL and 10 mg/mL Schisandra chinensis polysaccharide solution （0.2 mL/10 g）, respectively. Mice from the Kangnaoling group were intragastrically infused with 35 mg/mL Kangnaoling suspension （0.2 mL/10 g）, and the mice in the model group were intragastrically infused with the same volume of normal saline （0.2 mL/10 g） once per day for 30 consecutive days. MAIN OUTCOME MEASURES： Two hours after the final administration, pathohistological changes in the cerebral cortex and hippocampus were observed using hematoxylin ＆ eosin staining. AChE activity was detected using chromatometry. Monoamine neurotransmitter content was measured using fluorimetry. Learning and memory was measured using the step down test and darkness avoidance test. RESULTS： Both Schisandra chinensis polysaccharide and Kangnaoling improved pathological injury to the cerebral cortex and hippocampus in a mouse model of brain aging. Compared with the blank control group, AChE activity and content of norepinephrine （NA）, dopamine （DA）, and 5-hydroxytryptamine （5-HT） were significantly decreased in the model group （P 〈 0.01 ）. In contrast, AChE activity and NA, DA, and 5-HT levels significantly increased in the Kangnaoling and high dosage Schisandra chinensis polysaccharide groups （P 〈 0.01）, while NA levels significantly increased in the low dosage Schisandra chinensis polysaccharide group （P 〈 0.01）. Drug treatment improved learning and memory abilities （P 〈 0.01 or P 〈 0.05）. CONCLUSION： Schisandra chinensis polysaccharide significantly increased levels of central neurotransmitters and improved learning and memory in a mouse model of brain aging. The effects of Schisandra chinensis polysaccharide were equal to that of Kangnaoling pellets.

Correlation between changes of central neurotransmitter expression and stress response in mice A restraint time-course analysis

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.

Altered serous levels of monoamine neurotransmitter metabolites in patients with refractory and non-refractory depression

The study examined plasma metabolite changes of monoamine neurotransmitters in patients with treatment-resistant depression （TRD） and non-TRD before and after therapy. All 30 TRD and 30 non-TRD patients met the diagnostic criteria for a depressive episode in accordance with the International Classification of Diseases, Tenth Revision. Before treatment, and at 4, 6, and 8 weeks after treatment, the plasma metabolite products of monoamine neurotransmitters in TRD group, including 5-hydroxyindoleacetic acid, 3-methoxy-4-hydroxyphenyl ethylene glycol and homovanillic acid, were significantly lower than those in the non-TRD group. After two types of anti-depressive therapy with 5-serotonin and norepinephrine reuptake inhibitor, combined with psychotherapy, the Hamilton Depression Rating Scale scores were significantly reduced in both groups of patients, and the serous levels of 5-hydroxyindoleacetic acid and 3-methoxy-4-hydroxyphenyl ethylene glycol were significantly increased. In contrast, the homovanillic acid level exhibited no significant change. The levels of plasma metabolite products of peripheral monoamine neurotransmitters in depressive patients may predict the degree of depression and the therapeutic effects of treatment.

Effects of Subchronic Aluminum Exposure on Amino Acids Neurotransmitters in Chicken Brain

To investigate the effects of aluminium （Al） exposure on amino acid neurotransmitters, the chickens with different levels of subchronic Al poisoning were estabolished by continuous peritoneal injection of fixed volume and different concentrations of gradient of aluminium trichloride （AlCl3）. The levels of amino acid neurotransmitters in chicken brains were determined by high performance liquid chromatography （HPLC） after being exposed of Al for 60 days, and Al levels in serum and brain tissue were determined by atomic absorption spectrophotometry （AAS）. The results showed that Glu levels increased with the increase of Al, but there was no significant difference compared with the control. The levels of Al, Asp, Gly, GABA and Tau were significantly higher in Al-treated groups than those in the control. The results indicated that Al intoxication led to excitatory neurotoxicity.

Effects of Fuhe decoction on behaviors and monoamine neurotransmitters in different brain regions of CUMS combined with social isolation depression model rats

Objective:To investigate the effect of Fuhe decoction on the behavior and levels of monoamine neurotransmitters in different brain regions in a depression rat model induced by chronic unpredictable mild stimulation(CUMS)combined with social isolation.Methods:Fifty male SD rats were randomly divided into a blank group,model group,fluoxetine group,Chaiqinwendan decoction group,and Fuhe decoction group.Chronic unpredictable mild stimulation combined with a social isolation method was used to replicate the depression rat model.After 42 days of administration,a tail suspension test and high-performance liquid electrochemical detection(HPLC-ECD)were used to detect the behavioral changes and changes in the content of monoamine neurotransmitters norepinephrine(NE),dopamine(DA),5-hydroxytrytamine(5-HT),and metabolites in different brain regions of rats in each group before and after treatment.Results:Compared with the model group,the epinephrine(E)content in the Fuhe decoction group was highly significantly increased(P<.01).Compared with the model group,the 5-HT content of the prefrontal cortex in rats in the Fuhe decoction group was highly significantly increased(P<.01).Furthermore,compared with the model group,the 5-HT content in the hippocampus of rats in the Fuhe decoction group was significantly increased(P<.05).Conclusion:Fuhe decoction can improve the depression-like behaviors of model rats,and its antidepressant effect may be related to the increase in 5-HT content in the prefrontal cortex and hippocampus of rats.