Effects of the NMDA-antagonist,MK-801, on stress-induced alterations of dopamine dependent behavior

The effects of pretreatment with the non-competitive NMDA antagonist (+)MK-801 on the behavioral alterations induced by repeated restraint stress were investigated. Repeatedly stressed (restraint stress 2 h a day × 10 days) mice showed enhanced sensitivity to the inhibitory effects of a low dose of direct dopamine agonist, apomorphine (0.25 mg/kg), on climbing behavior. On the other hand, no changes were observed for the stimulatory effect of the high dose of apomorphine (3 mg/kg) on this behavioral response. Mice pretreated with MK-801 (0.15 mg/kg) before the stressful experience did not show altered response to the low dose of apomorphine (0.25 mg/kg). Finally, ten daily injections with 0.15 mg/kg MK-801 did not affect the behavioral response to the low dose of apomorphine, but enhanced the stimulatory effect of the high dose of the dopaminergic agonist on climbing behavior. Therefore, it is possible that the protective action of MK-801 against stress-induced behavioral alteration is due to changes in sensitivity of postsynaptic receptors.     

Antipsychotics increase vesicular glutamate transporter 2 (VGLUT2) expression in thalamolimbic pathways

Recently the two vesicular-glutamate-transporters VGLUT1 and VGLUT2 have been cloned and characterized. VGLUT1 and VGLUT2 together label all glutamatergic neurons, but because of their distinct expression patterns in the brain they facilitate our ability to define between a VGLUT1-positive cortical and a VGLUT2-positive subcortical glutamatergic systems. We have previously demonstrated an increased cortical VGLUT1 expression as marker of antidepressant activity. Here, we assessed the effects of different psychotropic drugs on brain VGLUT2 mRNA and protein expression. The typical antipsychotic haloperidol, and the atypicals clozapine and risperidone increased VGLUT2 mRNA selectively in the central medial/medial parafascicular, paraventricular and intermediodorsal thalamic nuclei; VGLUT2 protein was accordingly amplified in paraventricular and ventral striatum and in prefrontal cortex. The antidepressants fluoxetine and desipramine and the sedative anxiolytic diazepam had no effect. These results highlight the implication of thalamo-limbic glutamatergic pathways in the action of antipsychotics. Increased VGLUT2 expression in these neurons might constitute a marker for antipsychotic activity and subcortical glutamate neurotransmission might be a possible novel target for future generation antipsychotics.     

应用磁共振波谱研究针刺合谷穴前额叶神经递质Glu与GABA相关性＊

目的 探讨手针针刺健康受试者右侧合谷穴，前额叶Glu⁺、Glx⁺及GABA⁺浓度变化差异及相关性，从兴奋和抑制性神经递质关系方面初步探讨针刺效应的脑机制。方法 录入健康志愿者76名，随机接受手针及纤毛针两种刺激，并采集刺激前和刺激时BOLD功能磁共振脑成像（fMRI）及磁共振波谱（MRS）数据，分析手针和纤毛针组刺激前与刺激时Glu⁺、Glx⁺、GABA⁺浓度差异及相关性，以及Glu⁺、Glx⁺与GABA⁺浓度的相关性。结果 手针及纤毛针组间和组内各亚组（依据不同BOLD信号）针刺前与针刺时Glu⁺、Glx⁺、GABA⁺浓度差异无统计学意义（P均>0.05）。但手针组整组的Glu⁺、Glx⁺、GABA⁺，零、负激活亚组的Glu⁺、Glx⁺和零激活GABA⁺针刺前与针刺时浓度呈正相关（P均<0.05）。针刺前手针组整组、零、负激活亚组的Glu⁺、Glx⁺均与GABA⁺呈正相关q（P均<0.05）；纤毛针组整组、正、负激活亚组Glu⁺、Glx⁺均与GABA⁺及零激活Glu⁺与GABA⁺均呈正相关（P均<0.05）；针刺时手针组整组、负激活亚组Glu⁺与GABA⁺呈正相关，零激活亚组Glx⁺与GABA⁺呈正相关（P均<0.05）。结论 针刺前与针刺时Glu⁺、Glx⁺与GABA⁺多呈正相关，可作为针刺脑机制研究的神经递质观察指标。     

Short-Term Visual Experience Leads to Potentiation of Spontaneous Activity in Mouse Superior Colliculus

Spontaneous activity in the brain maintains an internal structured pattern that reflects the external environment,which is essential for processing information and developing perception and cognition.An essential prerequisite of spontaneous activity for perception is the ability to reverberate external information,such as by potentiation.Yet its role in the processing of potentiation in mouse superior colliculus(SC)neurons is less studied.Here,we used electrophysiological recording,optogenetics,and drug infusion methods to investigate the mechanism of potentiation in SC neurons.We found that visual experience potentiated SC neurons several minutes later in different developmental stages,and the similarity between spontaneous and visually-evoked activity increased with age.Before eye-opening,activation of retinal ganglion cells that expressed ChR2 also induced the potentiation of spontaneous activity in the mouse SC.Potentiation was dependenton stimulus number and showed feature selectivity for direction and orientation.Optogenetic activation of parvalbumin neurons in the SC attenuated the potentiation induced by visual experience.Furthermore,potentiation in SC neurons was blocked by inhibiting the glutamate transporter GLT1.These results indicated that the potentiation induced by a visual stimulus might play a key role in shaping the internal representation of the environment,and serves as a carrier for short-term memory consolidation.     

卒中后抑郁新的病因假说——谷氨酸能障碍

卒中后抑郁（post-stroke depression,PSD）是卒中后常见的神经精神症状之一,以心境低落、 兴趣下降为主要特征,不仅影响患者神经功能的康复,而且显著增加卒中病死率。其发病机制尚未 明确,伴随离子型谷氨酸受体拮抗剂氯胺酮的快速抗抑郁作用的出现,谷氨酸（glutamate,Glu）能神 经系统在抑郁症及PSD中的作用日益突出,也为抗抑郁治疗带来新的契机。     

谷氨酸对原代培养海马神经细胞兴奋毒作用的研究

为更清楚地了解药物对神经元的损伤和保护作用，在体外对新生大鼠（０～１ｄ）海马神经细胞进行原代培养，建立了谷氨酸对原代培养海马神经细胞兴奋性神经毒损伤模型。通过检测神经细胞乳酸脱氢酶泄漏率和在相差显微镜下对神经细胞形态变化的观察，发现只有发育成熟的神经元对谷氨酸兴奋毒损伤最敏感，神经元的兴奋毒损伤对谷氨酸在一定范围内有剂量依赖性或接触时间依赖性关系，提示谷氨酸通过与其受体结合造成神经元兴奋毒损伤。     

加味四逆散对皮质酮、谷氨酸致PC12细胞损伤的保护作用研究

目的:观察中药加味四逆散(Jiawei Sinisan,JWSNS)对皮质酮(corticOSterone,Cort)、谷氨酸(glutamate,Glu)致PC12细胞损伤的保护作用.方法:以100,200,400 μmol/L Cort和10,50,100 μmol/L Glu以及50,100 ml/L JWSNS含药血清分别与PC12细胞共同孵育24 h,采用倒置显微镜观察细胞形态,以甲基噻唑基四唑(methyl thiazolyl tetrazolium,MTT)法测定细胞存活率.选取200 μmol/L Cort和50 μmol/L Glu建立PC12细胞损伤模型,以MTT法观察50,100ml/L JWSNS含药血清各组对Cort和Glu所致PC12细胞损伤的保护作用.结果:不同浓度的Cort和Glu对PC12细胞的生长均具有抑制作用,随着浓度的升高,细胞损伤程度加重.各浓度的JWSNS含药血清对正常PC12细胞无毒性和不良反应.对Cort和Glu所致的PC12细胞模型,50ml/L JWSNS含药血清各组无明显抗损伤作用;Cort,Glu 100 ml/L JWSNS含药血清低、中、高各组细胞存活率分别为72.58%、87.11%、75.81%、69.35%、82.25%和70.97%,与Cort、Glu损伤模型组及正常血清组相比,细胞存活率明显升高,差异有显著性(P＜0.05,P＜0.01).结论:100ml/L JWSNS含药血清对Cort、Glu所致PC12细胞的损伤具有保护作用.     

八肽胆囊收缩素对谷氨酸神经毒性的拮抗作用

目的：探讨八肽胆囊收缩素（ＣＣＫ－８）对谷氨酸神经兴奋毒性的作用。方法：采用神经元原代分离培养技术，应用电镜观察经不同药物处理后的大鼠大脑皮层神经元的形态学变化，同时测定细胞上清液中ＬＤＨ活性值，并进行ｔ检验等统计学分析。结果：ＣＣＫ－８能明显改善由谷氨酸诱导的神经元结构的破坏和减少神经元损伤后ＬＤＨ的释放，该作用可被ＣＣＫ＿Ｂ受体拮抗剂阻断。结论：ＣＣＫ－８可通过Ｂ受体介导产生对谷氨酸神经毒性的拮抗作用。     

Functional Connections of the Vestibulo-spino-adrenal Axis in the Control of Blood Pressure Via the Vestibulosympathetic Reflex in Conscious Rats

Significant evidence supports the role of the vestibular system in the regulation of blood pressure during postural movements. In the present study, the role of the vestibulo-spino-adrenal (VSA) axis in the modulation of blood pressure via the vestibulosympathetic reflex was clarified by immunohistochemical and enzyme immunoassay methods in conscious rats with sinoaortic denervation. Expression of c-Fos protein in the intermediolateral cell column of the middle thoracic spinal regions and blood epinephrine levels were investigated, following microinjection of glutamate receptor agonists or antagonists into the medial vestibular nucleus (MVN) and/or sodium nitroprusside (SNP)-induced hypotension. Both microinjection of glutamate receptor agonists (NMDA and AMPA) into the MVN or rostral ventrolateral medullary nucleus (RVLM) and SNP-induced hypotension led to increased number of c-Fos positive neurons in the intermediolateral cell column of the middle thoracic spinal regions and increased blood epinephrine levels. Pretreatment with microinjection of glutamate receptor antagonists (MK-801 and CNQX) into the MVN or RVLM prevented the increased number of c-Fos positive neurons resulting from SNP-induced hypotension, and reversed the increased blood epinephrine levels. These results indicate that the VSA axis may be a key component of the pathway used by the vestibulosympathetic reflex to maintain blood pressure during postural movements.