5-羟色胺对正常大鼠丘脑底核神经元放电的双向效应

目的观察5-HT对正常大鼠丘脑底核神经元放电频率的影响及其作用机制。方法用多管微电极在体细胞外电生理记录观察5-HT及5-HT1B、5-HT2C、5-HT4和5-HT1A受体激动剂对丘脑底核神经元的电生理效应,免疫组织化学法观察丘脑底核神经元4种受体亚型的表达情况。结果 5-HT既可使丘脑底核神经元的自发放电频率明显升高(P0.001),也可使其明显降低(P0.05)。作为5-HT受体激动剂,CP-93129、RO-600175和ML-10302可明显增加丘脑底核神经元的放电频率(CP-93129:P0.001;RO-600175:P0.01;ML-10302:P0.001),8-OHDPAT则使其放电频率明显降低(P0.01)。正常大鼠丘脑底核表达丰富的5-HT1B、5-HT2C、5-HT4和5-HT1A受体。结论 5-HT可以改变正常大鼠丘脑底核神经元的兴奋性,产生使放电频率升高和降低的双向效应。5-HT的这种兴奋效应主要是通过激活5-HT1B、5-HT2C和5-HT4受体实现的,而抑制效应则与5-HT1A受体的激活有关。     

帕金森氏病病人丘脑底核的电生理特性及深部脑刺激的研究

目的　研究帕金森氏病 (PD)病人丘脑底核 (STN)的电生理特性及深部脑刺激 (DBS)对PD的治疗作用 ,观察术中STN电刺激对PD病人的震颤、肌僵直、运动缓慢的缓解及对语言感觉的影响。方法　在 2 6例立体定向术治疗PD手术中 ,应用美国FHC公司生产的微电极记录系统 ,记录病人STN不同部位的放电形式 ;并在MRI和微电极导向下 ,将刺激电极植入STN ,进行刺激实验 ;高频刺激参数的频率是 1 50Hz,脉宽 1 50ms,强度自 0 .5V开始 ,逐渐增加至6～ 8V ;其中 2例进行了STN的永久性DBS ,术后分别随访 1 4个月和 1 8个月。结果　微电极进入STN ,可记录到一致的、稳定的高频放电〔8～ 1 0V、(96± 1 6)Hz〕 ;术中刺激发现 ,在最佳点位刺激 ,病人的震颤、肌僵直、运动缓慢均得到明显改善 ,1 1例病人 (42 % )在刺激强度增加到 4～ 6V以上时 ,有语言障碍。结论　微电极记录获得STN的电生理放电特征 ,可以提高立体定向治疗PD的靶点精确性 ,提高疗效 ;STN的高频刺激能改善PD的震颤、肌僵直、运动缓慢等主要症状 ,是DBS治疗PD的最佳靶点之一。     

一氧化氮对大鼠黑质致密部神经元自发放电及Glu能和GABA能传入活动的影响

目的:研究一氧化氮(NO)对大鼠黑质致密部(SNc)神经元自发放电活动及对谷氨酸(Glu)、γ-氨基丁酸(GABA)能神经纤维输入活动的影响,为进一步研究Parkinson病(PD)的发病机制奠定神经生理学基础。方法:采用微电泳技术观察NO供体硝普钠(SNP),Glu及GABA对SNc神经元自发放电活动的影响及神经递质间的相互作用。结果:微电泳SNP使81.25%(39/48)受试神经元自发放电频率加快,此兴奋性作用与微电泳电流强度正相关,随着电流强度的增加(20nA～80nA),SNc神经元自发放电频率进一步加快。在35个受试神经元上分别微电泳Glu或GABA后,可以观察到分别有31神经元兴奋或所有神经元表现为抑制作用。在已经被Glu兴奋的31个神经元上同时微电泳SNP可使SNc神经元自发放电频率进一步加快。相反,在微电泳GABA的同时应用SNP可使已经被抑制的神经元放电频率增加。结论:NO对SNc神经元产生兴奋性作用。NO与Glu、GABA能投射在SNc有汇聚作用,NO协同Glu对SNc神经元产生兴奋性作用,但拮抗GABA对SNc神经元抑制性作用。     

电刺激大鼠小脑顶核对下丘脑神经元放电活动的影响

目的:研究电刺激小脑顶核(fastigial nucleus,FN)及微电泳Glu(glutamic acid)、MK-801对大鼠下丘脑(hypothalamus,HT)神经元自发放电活动的影响,探讨电刺激FN治疗脑卒中大鼠的机制。方法:应用细胞外记录的方法,记录电刺激FN及微电泳药物对HT神经元放电的影响。结果:电刺激频率为20Hz(低频)时,50%的HT神经元的放电频率增高(P0.01),电刺激频率为100Hz(高频时),80%的HT神经元的放电频率增高(P0.01);Glu对HT有紧张性兴奋作用,其拮抗剂MK-801能够明显抑制Glu诱致的兴奋作用;70%HT神经元在微电泳MK-801的基础上进行100Hz电刺激FN时,高频刺激诱发的兴奋作用被明显削弱。结论:采用电刺激FN治疗脑卒中,其可能机制是通过Glu的兴奋作用来调节HT的异常活动。     

PARP抑制剂3-AB对脂多糖诱导的帕金森病大鼠血脑屏障及多巴胺能神经元的影响

目的研究多聚ADP核糖聚合酶(poly(ADP-ribose)polymerase,PARP)抑制剂3-氨基苯甲酰(3-aminobenzamide,3-AB)对脂多糖(lipopolysaccharide,LPS)诱导的帕金森病(Parkinson's disease,PD)大鼠的血脑屏障(blood–brain barrier,BBB)及多巴胺能神经元的影响。方法大鼠随机分三组:对照组,LPS组和LPS+3-AB组。用伊文思兰渗透性实验检测血脑屏障通透性;Western blot法检测MMP-9和紧密连接蛋白ZO-1的表达;免疫组化法检测MMP-9在黑质神经元的表达。结果与对照组比较,LPS组黑质内BBB的通透性和MMP-9的表达显著增加,紧密连接蛋白相关蛋白ZO-1的表达和酪氨酸羟化酶(tyrosine hydroxylase,TH)阳性细胞数显著降低。上述作用受到PARP抑制剂3-AB的显著抑制。结论 3-AB通过保护LPS诱导的PD大鼠的BBB进一步保护多巴胺能神经元。     

腺苷对大鼠缰核神经元自发放电活动及c-fos蛋白表达的影响

目的:观察腺苷(Adenosine,Ado)对缰核(Habenula nucleus,Hb)神经元单位放电的影响及外侧缰核内c-fos蛋白表达的变化,探讨腺苷对影响睡眠的缰核神经元活动及相关基因表达的影响及可能机制。方法:脑薄片灌注、腹腔内注射、原位免疫细胞化学等。结果:脑薄片灌注腺苷,导致内侧缰核神经元自发放电活动受到抑制,而外侧缰核神经元自发放电活动明显增加;腹腔注射腺苷0.5小时后,与注射生理盐水组相比较,外侧缰核c-fos蛋白的表达量明显增加。结论:腺苷对大鼠内侧缰核神经元自发放电起抑制作用,对外侧僵核神经元自发放电则有兴奋作用,并可促进外侧缰核c-fos蛋白表达,这为腺苷在外侧缰核内可促进睡眠提供了依据。     

反义nov基因对培养神经元神经递质分泌的影响

目的：研究nov基因在神经元功能分化和神经递质分泌中的作用。方法：利用反义核酸技术构建成反义nov基因真核表达载体pBK-nov。采用脂质体转染技术,交坂义表达载体导入培养的大鼠大脑皮质神经元和纹状体神经元,经G418筛选出被转染的神经元继续培养,RT－PCR检测围染后nov mRNA的表达量。采用高效氨基酸分析仪和高效液相色说 ,检测抑制表达后氨基酸类递质和多巴胺类递质的变化。结果：谷氨酸和肾上腺素的分泌量明显下降,γ－氨基酸上升,而对多巴胺的分泌没有显著的影响。结论以上结果提示,nov基因在中枢神经系统神经递质的生成释放和代谢中起作用,可能籍此调节神经系统的功能。     

离体大鼠海马神经元自发放电活动一般特征的研究

观察离体大鼠海马锥体细胞的生理电发放模式.在脑脊液孵育下,将玻璃微电极插入到离体大鼠海马脑片锥体细胞附近,进行胞外电脉冲记录,微机记录并保存电信号.共观察到海马部神经元自发放电主要呈5种特征,分别为不规则发放、单波规则发放、紧张发放、阵发排放及周期排放型等形式.说明神经元的生理电发放模式可能与细胞的排列次序、生理应答呈一定的相关性.     

脉冲磁场对大鼠记忆能力和海马神经递质的影响

本文用低频脉冲磁场和被调制的高频脉冲磁场刺激大鼠，研究不同磁场对大鼠记忆能力及脑内神经递质的影响，探讨其作用机制。研究结果表明，高频脉冲磁场和低频脉冲磁场对大鼠的记忆能力都产生明显影响，但随着时间延长，这种影响逐渐消失；与对照组比较，刺激组大鼠海马去甲肾上腺素（NE）、多巴胺（DA）及5－羟色胺（5－HT）含量增加；乙酰胆碱（ACh）含量减少。脉冲磁场能够影响海马神经递质释放，降低大鼠记忆能力。     

神经营养因子对中脑黑质多巴胺能神经元的作用

神经营养因子对帕金森氏病等神经退行性疾病的治疗显示出诱人的前景。在对中脑黑质多巴胺能神经元有作用的神经营养因子当中 ,以胶质细胞系源性神经营养因子和脑源性神经营养因子的效应更强大。此外 ,中脑黑质多巴胺能神经元的主要靶区纹状体细胞以及该神经元局部的胶质细胞可产生对此神经元有作用的神经营养因子。本文概述了有关的研究成果 ,并对神经营养因子运用于帕金森氏病的治疗研究提出了展望     

GABAB and group I metabotropic glutamate receptors in the striatopallidal complex in primates

Glutamate and GABA neurotransmission is mediated through various types of ionotropic and metabotropic receptors. In this review, we summarise some of our recent findings on the subcellular and subsynaptic localisation of GABA_B and group I metabotropic glutamate receptors in the striatopallidal complex of monkeys. Polyclonal antibodies that specifically recognise GABA_BR1, mGluR1a and mGluR5 receptor subtypes were used for immunoperoxidase and pre‐embedding immunogold techniques at the light and electron microscope levels. Both subtypes of group I mGluRs were expressed postsynaptically in striatal projection neurons and interneurons where they aggregate perisynaptically at asymmetric glutamatergic synapses and symmetric dopaminergic synaptic junctions. Moreover, they are also strongly expressed in the main body of symmetric synapses established by putative intrastriatal GABAergic terminals. In the globus pallidus, both receptor subtypes are found postsynaptically in the core of striatopallidal GABAergic synapses and perisynaptically at subthalamopallidal glutamatergic synapses. Finally, extrasynaptic labelling was commonly seen in the globus pallidus and the striatum. Moderate to intense GABA_BR1 immunoreactivity was observed in the striatopallidal complex. At the electron microscope level, GABA_BR1 immunostaining was commonly found in neuronal cell bodies and dendrites. Many striatal dendritic spines also displayed GABA_BR1 immunoreactivity. Moreover, GABA_BR1‐immunoreactive axons and axon terminals were frequently encountered. In the striatum, GABA_BR1‐immunoreactive boutons resembled terminals of cortical origin, while in the globus pallidus, subthalamic‐like terminals were labelled. Pre‐embedding immunogold data showed that postsynaptic GABA_BR1 receptors are concentrated at extrasynaptic sites on dendrites, spines and somata in the striatopallidal complex, perisynaptically at asymmetric synapses and in the main body of symmetric striatopallidal synapses in the GPe and GPi. Consistent with the immunoperoxidase data, immunoparticles were found in the presynaptic grid of asymmetric synapses established by cortical‐ and subthalamic‐like glutamatergic terminals. These findings indicate that both GABA and glutamate metabotropic receptors are located to subserve various modulatory functions of the synaptic transmission in the primate striatopallidal complex. Furthermore, their pattern of localisation raises issues about their roles and mechanisms of activation in normal and pathological conditions. Because of their ‘modulatory’ functions, these receptors are ideal targets for chronic drug therapies in neurodegenerative diseases such as Parkinson's disease.     

Effect of Subthalamic Deep Brain Stimulation on Levodopa-Induced Dyskinesia in Parkinson's Disease

Purpose

To evaluate the effect of bilateral subthalamic nucleus (STN) deep brain stimulation (DBS) on levodopa-induced peak-dose dyskinesia in patients with Parkinson''s disease (PD).

Materials and Methods

A retrospective review was conducted on patients who underwent STN DBS for PD from May 2000 to July 2012. Only patients with levodopa-induced dyskinesia prior to surgery and more than 1 year of available follow-up data after DBS were included. The outcome measures included the dyskinesia subscore of the Unified Parkinson''s Disease Rating Scale (UPDRS) part IV (items 32 to 34 of UPDRS part IV) and the levodopa equivalent daily dose (LEDD). The patients were divided into two groups based on preoperative to postoperative LEDD change at 12 months after the surgery: Group 1, LEDD decrease >15%; Group 2, all other patients. Group 2 was further divided by the location of DBS leads.

Results

Of the 100 patients enrolled, 67 were in Group 1, while those remaining were in Group 2. Twelve months after STN DBS, Groups 1 and 2 showed improvements of 61.90% and 57.14%, respectively, in the dyskinesia subscore. Group 1 was more likely to experience dyskinesia suppression; however, the association between the groups and dyskinesia suppression was not statistically significant (p=0.619). In Group 2, dyskinesia was significantly decreased by stimulation of the area above the STN in 18 patients compared to stimulation of the STN in 15 patients (p=0.048).

Conclusion

Levodopa-induced dyskinesia is attenuated by STN DBS without reducing the levodopa dosage.     

Effect of stimulation of subthalamic nucleus on grooming movements and their rhythmicity in pups and mature rats

The effect of rhythmic stimulation of subthalamic nucleus on grooming movements and their rhythmicity was studied on mature rats and on 13- and 14-day rat pups. Unilateral monopolar stimulation of subthalamic nucleus was performed on unrestrained animals via implanted electrodes. This stimulation activated virtually all grooming movements (scratching, hair-plucking, licking, and body-shaking); the effect was most pronounced in pups. Acceleration of the rhythm of grooming movements was observed only in rat pups for hair-plucking and scratching on the contralateral side relatively to the stimulated nucleus. In mature rats stimulation of the subthalamic nucleus prolonged grooming movements in most cases, but did not increase their number and rhythm. Translated fromByulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 138, No. 9, pp. 244–246, September, 2004     

Effect of stimulation of subthalamic nucleus on grooming movements and their rhythmicity in pups and mature rats

The effect of rhythmic stimulation of subthalamic nucleus on grooming movements and their rhythmicity was studied on mature rats and on 13- and 14-day rat pups. Unilateral monopolar stimulation of subthalamic nucleus was performed on unrestrained animals via implanted electrodes. This stimulation activated virtually all grooming movements (scratching, hair-plucking, licking, and body-shaking); the effect was most pronounced in pups. Acceleration of the rhythm of grooming movements was observed only in rat pups for hair-plucking and scratching on the contralateral side relatively to the stimulated nucleus. In mature rats stimulation of the subthalamic nucleus prolonged grooming movements in most cases, but did not increase their number and rhythm.Translated from Byulleten Eksperimentalnoi Biologii i Meditsiny, Vol. 138, No. 9, pp. 244–246, September, 2004     

高频电刺激大鼠丘脑底核抑制背侧中缝核5-羟色胺表达

本研究探讨高频电刺激丘脑底核对大鼠背侧中缝核5-羟色胺(5-HT)表达的影响。实验动物分两组,刺激组给予高频电流(130Hz,100μA,60μs)刺激大鼠右侧丘脑底核,对照组大鼠右侧丘脑底核植入电极,但无电流输出。刺激结束后,用免疫组织化学方法染色背侧中缝核5-HT能神经元,检测背侧中缝核5-HT能神经元的数量和平均灰度值。结果显示电刺激组背侧中缝核5-HT阳性神经元数目与对照组比明显减少(t(13)=3.786,P=0.002),并且神经递质5-HT表达量减少,平均灰度值显著增高(t(13)=7.917,P<0.001)。本实验结果表明高频电刺激丘脑底核对背侧中缝核5-HT能神经元有抑制作用,在应用高频电刺激丘脑底核治疗Parkison病运动障碍时出现的情绪障碍可能与其有关。     

Imaging of glutamate neurotransmitter alterations in Alzheimer's disease

Glutamate (Glu) is a major excitatory neurotransmitter in the brain and has been shown to decrease in the early stages of Alzheimer's disease (AD). Using a glutamate chemical (amine) exchange saturation transfer (GluCEST) method, we imaged the change in [Glu] in the APP‐PS1 transgenic mouse model of AD at high spatial resolution. Compared with wild‐type controls, AD mice exhibited a notable reduction in GluCEST contrast (~30%) in all areas of the brain. The change in [Glu] was further validated through ¹H MRS. A positive correlation was observed between GluCEST contrast and ¹H MRS‐measured Glu/total creatine ratio. This method potentially provides a novel noninvasive biomarker for the diagnosis of the disease in preclinical stages and enables the development of disease‐modifying therapies for AD. Copyright © 2012 John Wiley & Sons, Ltd.     

An in-silico model of the biosynthesis of neurotransmitter glutamate, elucidates the complex regulatory role of glucocorticoids in neurotransmitter glutamate release

An in-silico model, of the glucocorticoid regulated glutamate release, in rat hippocampal tissue, is constructed. The model permits the pseudo-steady state estimation of various fluxes, experimentally impossible to measure, from a set of measured rates. Estimates of the astrocytic pyruvate carboxylase reaction and the neuronal TCA cycle rates are correlated with different dexamethasone concentrations, in order to extrapolate explicit kinetic equations. The model suggests that the observed effects of glucocorticoids can be attributed to the inhibitory actions of dexamethasone on two competing pathways, that of the neuronal TCA cycle and the biosynthetic pathway of neurotransmitter glutamate.     

Biphasic modulation of spontaneous activities of entopeduncular neurons by systemic application of apomorphine in anesthetized cats

The responses of entopeduncular neurons to apomorphine were investigated with extracellular recording methods in anesthetized cats. Apomorphine was applied intravenously in increasing doses, which cumulatively doubled with each addition (5-640 micrograms/kg). The spontaneous firing rates of entopeduncular neurons, which were inhibited by electrical stimulation of the caudate nucleus, increased when lower doses of apomorphine (5-20 micrograms/kg) were applied. However, higher doses (40-640 micrograms/kg) produced a dose-dependent decrease in the firing rate. The results suggest that there are direct and indirect effects of systemically administered apomorphine on entopeduncular neurons which may contribute to biphasic responses in the spontaneous discharge rate.