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.

Relationship of serum neurotransmitters with anxiety depression, T lymphocyte subsets and NK cells in patients with lung cancer chemotherapy

Objective:To study the relationship of serum neurotransmitters with anxiety depression, T lymphocyte subsets and NK cells in patients with lung cancer chemotherapy.Methods: 56 cases of patients with advanced lung cancer who received chemotherapy in the First Affiliated Hospital of Chengdu Medical College between July 2013 and August 2016 were collected as observation group, and 50 healthy subjects who received physical examination in our hospital during the same period were selected as normal control group. Serum neurotransmitter, negative emotions and immune index levels were compared between the two groups of subjects. Pearson test was used to evaluate the relationship of serum neurotransmitter contents with negative emotions and immune index levels in patients with lung cancer chemotherapy. Results: Serum neurotransmitters DA, 5-HT and NE contents in observation group were lower than those in normal control group;SAS and SDS scores were higher than those of normal control group;peripheral blood CD4+T lymphocyte level, CD4+/CD8+ ratio and NK cell level were lower than those in normal control group while CD8+ T lymphocyte level was higher than that in normal control group. Pearson test showed that serum neurotransmitters DA, 5-HT and NE contents in patients with lung cancer chemotherapy were directly correlated with anxiety depression, T lymphocyte subset and NK cell levels.Conclusion: Serum neurotransmitter expression decrease in patients with lung cancer chemotherapy, and this is one of the important causes of anxiety depression and immune dysfunction in patients.

Effect of dialectical behavior therapy on the serum neurotransmitters and cytokines in depression patients with suicidal tendency

Objective: To explore the effect of dialectical behavior therapy on the serum neurotransmitters and cytokines in depression patients with suicidal tendency. Methods: A total of 98 depression patients with suicidal tendency who were treated in the hospital between August 2014 and August 2017 were collected and divided into the control group (n=49) and the research group (n=49) by random number table. Control group received routine drug therapy, and study group received dialectical behavior therapy combined with drug therapy. The differences in serum levels of monoamine neurotransmitters, nerve function indexes and acute phase proteins were compared between the two groups of patients. Results: After treatment, serum NE, 5-HT and DA levels of research group were higher than those of control group;serum MBP and NSE levels of research group were lower than those of control group while BDNF level was higher than that of control group;serum Tf level of research group was higher than that of control group while Hp level was lower than that of control group. Conclusion: Dialectical behavior therapy intervention can effectively optimize the nerve function and improve the overall state of depression patients with suicidal tendency.

Effect of adjuvant acupuncture therapy on serum cytokines and neurotransmitters in patients with post-stroke depression

Objective:To study the effect of adjuvant acupuncture therapy on serum cytokines and neurotransmitters in patients with post-stroke depression.Methods: Patients with poststroke depression who were treated in Traditional Chinese Medicine Hospital of Yuyang District Yulin City between May 2014 and February 2017 were selected as the research subjects and divided into two groups by random number table, control group of patients received neurotrophy, rehabilitation exercise, antidepressant drugs and other symptomatic treatment, and the acupuncture group received auxiliary acupuncture treatment on the basis of symptomatic treatment. The serum levels of nerve cytokines, inflammatory cytokines and neurotransmitters were detected before treatment as well as 2 weeks and 4 weeks after treatment.Results: 2 weeks and 4 weeks after treatment, serum BDNF, NGF, IGF-1, FGF-2, NE, DA and 5-HT levels of both groups of patients were higher than those before treatment while HCY, IL-1β, IL-2, sIL-2R, TNF-α levels were lower than those before treatment, and serum BDNF, NGF, IGF-1, FGF-2, NE, DA and 5-HT levels of acupuncture group were higher than those of control group while HCY, IL-1β, IL-2, sIL-2R, TNF-α levels were lower than those of control group.Conclusion: Adjuvant acupuncture therapy for post-stroke depression can increase the secretion of nerve cytokines, reduce the secretion of inflammatory cytokines and regulate the function of monoamine neurotransmitters.

Effect of anxiety and depression on serum neurotransmitters and immune function in patients with cervical cancer chemotherapy

Objective:To study the effect of anxiety and depression on serum neurotransmitters and immune function in patients with cervical cancer chemotherapy.Methods:Patients with advanced cervical cancer who received chemotherapy in the First Affiliated Hospital of Chengdu Medical College between May 2014 and June 2016 were selected, HAMA scores and HAMD scores were used to assess anxiety and depression and divide the patients into control group, depression group, anxiety group and depression + anxiety group. The contents of monoamine neurotransmitters and immune cytokines in serum as well as the expression of immune transcription factors in peripheral blood mononuclear cells were detected.Results:Serum NE, E, 5-HT, 5-HIAA and DOPAC contents of depression group and depression + anxiety group were significantly lower than those of control group, and serum NE, E, 5-HT, 5-HIAA and DOPAC contents of anxiety group were significantly higher than those of control group;peripheral blood T-bet mRNA expression as well as serum IFN-γ and TNF-α contents of depression group, anxiety group and depression + anxiety group were significantly lower than those of control group while GATA3, Foxp3 and RORγt mRNA expression as well as serum IL-4, TGF-β and IL-17 contents were significantly higher than those of control group;peripheral blood T-bet mRNA expression as well as serum IFN-γ and TNF-α contents of depression + anxiety group were significantly lower than those of depression group and anxiety group while GATA3, Foxp3 and RORγt mRNA expression as well as serum IL-4, TGF-β and IL-17 contents were significantly higher than those of depression group and anxiety group. Conclusion: Anxiety and depression in patients with cervical cancer chemotherapy can affect the secretion of monoamine neurotransmitters, the differentiation of CD4+T cell subsets and the antitumor immune response mediated by them.

Influence of hyperbaric oxygen combined with psychotropic drugs on serum neurotransmitter and cytokine contents in patients with post-stroke depression

Objective: To investigate the influence of hyperbaric oxygen combined with psychotropic drugs on serum neurotransmitter and cytokine contents in patients with post-stroke depression. Methods: A total of 62 patients with post-stroke depression who were treated in the hospital between January 2015 and February 2017 were divided into routine group (n=31) and hyperbaric oxygen group (n=31) by random number table method. Routine group received antidepressant therapy, hyperbaric oxygen group received hyperbaric oxygen combined with antidepressant therapy, and the therapies lasted for 8 weeks. The differences in the serum contents of monoamine neurotransmitters, inflammatory factors and oxidative stress indexes were compared between the two groups before and after treatment. Results: There was no statistically significant difference in serum levels of monoamine neurotransmitters, inflammatory factors and oxidative stress indexes between the two groups before treatment. After 8 weeks of treatment, serum monoamine neurotransmitters NE, 5-HT and DA contents of hyperbaric oxygen group were higher than those of routine group;serum inflammatory factors IL-1, IL-6, IL-8 and hs-CRP contents were lower than those of routine group;serum oxidative stress indexes LHP and MDA contents were lower than those of routine group whereas CAT and GSH-Px contents were higher than those of routine group. Conclusion:Hyperbaric oxygen combined with psychotropic drug therapy can effectively increase the expression of monoamine neurotransmitters and balance the homeostasis in patients with post-stroke depression.

Effect of oxycodone hydrochloride injection preemptive analgesia on serum inflammatory factors, neurotransmitter index and immune function in patients with laparoscopic cholecystectomy

Objective:To investigate the effect of oxycodone hydrochloride injection preemptive analgesia on serum inflammatory factors, neurotransmitter index and immune function in patients with laparoscopic cholecystectomy.Methods: According to random data table, 113 patients undergoing laparoscopic cholecystectomy were divided into control group (n=57) and observation group (n=56), patients in the control group were treated with sufentanil citrate injection analgesia, and the observation group patients were given oxycodone hydrochloride injection analgesia, level of serum inflammatory factors [tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6)], neurotransmitter index [5-hydroxy tryptamine (5-HT), P substance] and immune function index [CD4+, CD8+, CD4+/CD8+] of two groups between preoperative and postoperative 1d were compared.Results: There were no significant difference in level of TNF-α, IL-6, 5-HT, P substance, CD4+, CD8+ and CD4+/CD8+ between the two groups preoperative. Compared with the level of the same group preoperative, at postoperative 1 d level of TNF-α, IL-6, 5-HT, P substance, CD8+were significantly increased, moreover level in the observation group were significantly lower compared with the control group, the difference was statistically significant;Postoperative 1 d, level of CD4+, CD4+/CD8+ in the two groups were significantly lower than the preoperative level within the group, and the observation group was significantly higher than the control group.Conclusion: Oxycodone hydrochloride injection preemptive analgesia in laparoscopic cholecystectomy can effectively reduce serum inflammatory factors and neurotransmitter index release, improve immune function, has an important clinical value.

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 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.

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.

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.

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.

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.

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.

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.

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.

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.