D-半乳糖联合对氯苯丙氨酸致肾不藏志不寐大鼠下丘脑神经递质和凋亡基因的实验研究

目的:观察D-半乳糖联合对氯苯丙氨酸(PCPA)致肾不藏志不寐大鼠下丘脑神经递质和凋亡基因的变化。方法:40只SD大鼠随机分为对照组、老年组、失眠组、肾不藏志不寐组(模型组),每组10只。老年组大鼠给予D-半乳糖皮下注射,失眠组给予对PCPA腹腔注射,肾不藏志不寐组给予D-半乳糖皮下注射联合PCPA腹腔注射建立模型,对照组给予等剂量生理盐水注射。造模结束后测量各组大鼠体质量、采用水迷宫观察大鼠定位航行探索运动轨迹、采用RT-PCR法检测各组大鼠下丘脑GABAARα1、GABAARβ2、GABAARγ2、Bax、Bcl-2 mRNA的相对表达量。结果:与空白组比较,模型组体质量显著降低(P<0.01);定位航行探索运动轨迹显著延长;模型组下丘脑GABAARα1、GABAARβ2、GABAARγ2、Bcl-2mRNA相对表达量均显著性降低(P<0.05,P<0.05,P<0.01,P<0.05);下丘脑Bax mRNA相对表达量显著性增加(P<0.05)。结论:D-半乳糖联合PCPA致肾不藏志不寐大鼠下丘脑睡眠相关的神经递质和凋亡基因表达发生改变。     

The influence of aripiprazole and olanzapine on neurotransmitters level in frontal cortex of prenatally stressed rats

ObjectivesThe study aims to verify whether alterations in the level of neurotransmitters have occurred in prenatally stressed rats (animal model of schizophrenia), and whether aripiprazole (ARI) and olanzapine (OLA) modify this level.MethodsThe effects of ARI (1.5 mg/kg) and OLA (0.5 mg/kg) were studied by means of microdialysis in freely moving rats (observation time 120 min). The level of neurotransmitters (DA, 5-HT, NA) and their metabolites (DOPAC, HVA, 5-HIAA) was analyzed by HPLC with coulochemical detection.ResultsObtained results indicate that after a single administration of ARI and OLA in the prenatally stressed rats the increase of DA, DOPAC, and 5-HT was observed. In turn ARI administration increase the level of HVA and 5-HIAA and also decrease the level of NA. After OLA administration the level of NA and HVA increased and no significant change in 5-HIAA was observed.ConclusionAlterations observed as a result of ARI and OLA administration may be pivotal in identifying animal models of mental disorders and in the analysis of neuroleptics effectiveness.     

Graphene oxide-induced neurotoxicity on neurotransmitters,AFD neurons and locomotive behavior in Caenorhabditis elegans

Graphene oxide (GO) and graphene-based nanomaterials have been widely applied in recent years, but their potential health risk and neurotoxic potentials remain poorly understood. In this study, neurotoxic potential of GO and its underlying molecular and cellular mechanism were investigated using the nematode, Caenorhabditis elegans. Deposition of GO in the head region and increased reactive oxygen species (ROS) was observed in C. elegans after exposure to GO. The neurotoxic potential of GO was then investigated, focusing on neurotransmitters contents and neuronal activity using AFD sensory neurons. The contents of all neurotransmitters, such as, tyrosine, tryptophan, dopamine, tyramine, and GABA, decreased significantly by GO exposure. Decreased fluorescence of Pgcy-8:GFP, a marker of AFD sensory neuron, by GO exposure suggested GO could cause neuronal damage on AFD neuron. GO exposure led decreased expression of ttx-1 and ceh-14, genes required for the function of AFD neurons also confirmed possible detrimental effect of GO to AFD neuron. To understand physiological meaning of AFD neuronal damage by GO exposure, locomotive behavior was then investigated in wild-type as well as in loss-of-function mutants of ttx-1 and ceh-14. GO exposure significantly altered locomotor behavior markers, such as, speed, acceleration, stop time, etc., in wild-type C. elegans, which were mostly rescued in AFD neuron mutants. The present study suggested the GO possesses neurotoxic potential, especially on neurotransmitters and AFD neuron in C. elegans. These findings provide useful information to understand the neurotoxic potential of GO and other graphene-based nanomaterials, which will guide their safe application.     

Histamine-4 receptor antagonist ameliorates Parkinson-like pathology in the striatum

Growing evidence indicates that microglia activation and a neuroinflammatory trigger contribute to dopaminergic cell loss in Parkinson’s disease (PD). Furthermore, increased density of histaminergic fibers and enhanced histamine levels have been observed in the substantia nigra of PD-postmortem brains. Histamine-induced microglial activation is mediated by the histamine-4 receptor (H₄R). In the current study, gene set enrichment and pathway analyses of a PD basal ganglia RNA-sequencing dataset revealed that upregulation of H₄R was in the top functional category for PD treatment targets. Interestingly, the H₄R antagonist JNJ7777120 normalized the number of nigrostriatal dopaminergic fibers and striatal dopamine levels in a rotenone-induced PD rat model. These improvements were accompanied by a reduction of α-synuclein-positive inclusions in the striatum. In addition, intracerebroventricular infusion of JNJ7777120 alleviated the morphological changes in Iba-1-positive microglia and resulted in a lower tumor necrosis factor-α release from this brain region, as well as in ameliorated apomorphine-induced rotation behaviour. Finally, JNJ7777120 also restored basal ganglia function by decreasing the levels of γ-aminobutyric acid (GABA) and the 5-hydroxyindoleactic acid to serotonin (5-HIAA/5-HT) concentration ratios in the striatum of the PD model. Our results highlight H₄R inhibition in microglia as a promising and specific therapeutic target to reduce or prevent neuroinflammation, and as such the development of PD pathology.     

Dynamic of neurochemical alterations in striatum,hippocampus and cortex after the 6-OHDA mesostriatal lesion

Immediate neurochemical alterations produced by 6-OHDA could explain the general toxic pattern in the central nervous system. However, no evidences describe the effects of 6-OHDA on early changes of neurotransmitters in rats’ striatum, cortex and hippocampus. In our study, unilateral 6-OHDA injection into medial forebrain bundle (MFB) was used in rats, then five neurotransmitters were analyzed at 3, 6, 12, 24, 48 and 72 h, respectively. Results showed that 6-OHDA injection caused a sharp decline of striatal dopamine (DA) levels in the first 12 h followed by a further reduction between 12 and 48 h. However, striatal levels of homovanillic acid (HVA) were stable in the first 12 h and showed a marked reduction between 12 and 24 h. Striatal levels of 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) decreased linearly for 72 h, whereas levels of norepinephrine (NE) showed a slight reduction in the first 48 h, and returned back to normal afterwards. Striatal HVA/DA ratio increased significantly in the first 12 h, but 5-HIAA/5-HT ratio showed a sharp increase between 12 and 72 h. Besides, neurochemical alterations were also found in hippocampus and cortex, and the correlations of neurotransmitters were analyzed. Our study indicated that NE system had little influence in the early phase of 6-OHDA injection, moreover, early neurochemical alterations were involved with striatum, hippocampus and cortex.     

亚健康失眠人群脑内神经递质活动的脑电超慢涨落图表现

目的:探讨亚健康失眠人群的脑电超慢涨落图(EFG)表现。方法:应用EFG分析仪检测亚健康失眠人群的脑内神经递质活动变化情况及其脑功能状态表现。结果:脑内神经递质’-氨基丁酸、谷氨酸、5-羟色胺、乙酰胆碱、去甲肾上腺素及多巴胺的实测值都低于正常参考值,差异均具有显著性(P<0.05)。脑功能状态指数中的运动指数、兴奋抑制指数的实测值都高于正常参考值,差异均具有显著性(P<0.01),而血管舒缩指数的实测值则稍高于正常参考值,但差异无显著性(P>0.05)。结论:亚健康失眠者脑内主要神经递质均明显降低,其脑功能状态存在不同程度的异常。     

Extremely Low Frequency Magnetic Field Modulates the Level of Neurotransmitters

This study was aimed to observe that extremely low frequency magnetic field (ELF-MF) may be relevant to changes of major neurotransmitters in rat brain. After the exposure to ELF-MF (60 Hz, 2.0 mT) for 2 or 5 days, we measured the levels of biogenic amines and their metabolites, amino acid neurotransmitters and nitric oxide (NO) in the cortex, striatum, thalamus, cerebellum and hippocampus. The exposure of ELF-MF for 2 or 5 days produced significant differences in norepinephrine and vanillyl mandelic acid in the striatum, thalamus, cerebellum and hippocampus. Significant increases in the levels of serotonin and 5-hydroxyindoleacetic acid were also observed in the striatum, thalamus or hippocampus. ELF-MF significantly increased the concentration of dopamine in the thalamus. ELF-MF tended to increase the levels of amino acid neurotransmitters such as glutamine, glycine and γ -aminobutyric acid in the striatum and thalamus, whereas it decreased the levels in the cortex, cerebellum and hippocampus. ELF-MF significantly increased NO concentration in the striatum, thalamus and hippocampus. The present study has demonstrated that exposure to ELF-MFs may evoke the changes in the levels of biogenic amines, amino acid and NO in the brain although the extent and property vary with the brain areas. However, the mechanisms remain further to be characterized.     

智能障碍的癫痫患者血清单胺类神经递质的变化及意义

目的：研究智能障碍的癫痫患者血清单胺类神经递质的变化及，临床意义。方法：对78例癫痫患者利用韦氏成人智力量表（WAIS—RC）进行全量表智商（FIQ）测查后，将患者分为智能障碍组和非智能障碍组，对两组基本情况进行差异性分析，采用荧光分光光度计法测定其血清单胺类神经递质多巴胺（DA）、去甲肾上腺素（NA）和5-羟色胺（5-HT）的含量，并与32名健康对照者（对照组）比较。结果：智能障碍组和非智能障碍组的年龄、职业、文化程度、病程和发作类型构成相比差异均具有显著性（P〈0．01或P〈0．05）。非智能障碍组和对照组患者血清DA、NE和5-HT的含量差异均无显著性（P〉0．05），智能障碍各组患者血清DA、NE和5-HT的含量均显著低于非智能障碍组（P〈0.01），且随智能障碍加重呈逐渐下降的趋势。结论：癫痫患者智能障碍的发生与血清单胺类神经递质含量降低有关，并且其含量在一定程度上可作为判断癫痫患者智能状况的客观指标。     

Oxidative stress in schizophrenia patients treated with long-acting haloperidol decanoate

In this study the role of oxidative stress in schizophrenia was investigated by evaluating the relationship of oxidative stress markers with neurochemistry, psychopathology, and extrapyramidal symptoms. Antioxidant activity of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, and concentrations of malondialdehyde, protein carbonyls, nitrite, nitrate, glutathione, dopamine, noradrenaline, adrenaline, and serotonin were measured in 52 outpatients with DSM-IV diagnosis of schizophrenia treated with haloperidol decanoate. Psychopathology and extrapyramidal symptoms were assessed by positive and negative syndrome scale, global assessment of functioning, abnormal involuntary movement scale, Simpson Angus scale, and Barnes akathisia rating scale. Haloperidol dose was positively correlated with plasma protein carbonyls. Longer duration of illness was associated with decreased levels of glutathione peroxidase. Increased activity of superoxide dismutase was associated with increased levels of catalase, glutathione peroxidase, glutathione reductase and reduced glutathione, and decreased concentration of malondialdehyde, indicating joint action of various antioxidative systems. Increased levels of nitrite and noradrenaline were associated with decreased level of malondialdehyde. Akathisia was greater in patients with decreased catalase activity, indicating involvement of impaired antioxidant defense in developing extrapyramidal symptoms. These results confirm the hypothesis that oxidative stress is involved in pathophysiology of schizophrenia and severity of extrapyramidal symptoms.     

Apoptosis and astrogliosis perturbations and expression of regulatory inflammatory factors and neurotransmitters in acrylamide-induced neurotoxicity under ω3 fatty acids protection in rats

This study was aimed to investigate the potential ameliorative effects of omega-3 (ω3) fatty acids against acrylamide (ACR)-induced neurotoxicity. Thirty-two adult male Sprague Dawley rats were randomly assigned into four groups (n = 8) as follows: control, ω3 fatty acids (1000 mg/kg bwt/day orally), ACR-treated (50 mg/kg bwt/day IP) and ACR plus ω3 fatty acids group. Treatments were performed every other day for 21 consecutive days. ACR induced abnormal gait and elevated serum levels of proinflammatory cytokines (IL-6 and TNF-α), brain and spinal cord MDA levels and decreased brain and spinal cord GSH levels. Moreover, it reduced neurotransmitters (acetylcholine, GABA, serotonin and noradrenaline levels) and increased AChE activity in brain tissues. Histopathologically, ACR caused various degenerative changes, necrosis and glial cell activation in the cerebrum, cerebellum, hippocampus, spinal cord and sciatic nerve. Likewise, the histomorphometric analysis was constant with ACR-induced neurotoxicity. The ACR induced axonal atrophy and myelin disruption and decreased g-ratio of the sciatic nerve. Immunohistochemically, strong positive expressions of apoptotic marker caspase-3 and astroglial GFAP in the examined tissues were detected. Contrariwise, concurrent administration of ω3 fatty acids partially attenuated ACR impacts, as it improved the gait performance, reduced oxidative stress and pro-inflammatory cytokines, and modulate the levels of the neurotransmitters. It also ameliorated the intensity of ACR-induced histopathological and histomorphometric alterations within the examined nervous tissues. It could be concluded that ω3 fatty acids have antioxidant, anti-inflammatory and anti-apoptotic potentials against ACR neurotoxicity via suppression of oxidative stress, lipid peroxidation and pro-inflammatory cytokines, and inhibition of AChE activity and downregulation of caspase-3 and GFAP expressions in the nervous tissues.