电刺激听神经诱发小鼠脑干神经元活动的光信号及GABA能的作用

目的　 使用光学记录的方法观察小鼠脑干听神经电刺激诱发冲动的时间 空间分布 ,及抑制性神经递质GABA和GABAA受体拮抗剂荷包牡丹碱 (BMI)对听觉诱发冲动的影响。 方法　 使用出生后早期的 (0～ 5d)ddy/ddy小鼠 ,在冷冻条件下制作有活性的脑干切片 ;用电压敏感染料 (NK 30 4 1)做脑片染色 ;16× 16像素的硅光电二极管阵列 (16× 16pixelsSiliconPhotodiodeArray)设备用来记录刺激听神经所诱发的光学信号 ;观察GABA及竞争性GABAA受体拮抗剂BMI对听神经诱发信号的作用。 结果　 刺激听神经诱发的光学信号以时间 空间分布的形式被记录。每一个光学信号分为两个成分 :快的峰电位样反应及慢的长时程反应。快电位的起始相具有突触前性质 ,晚期相具有突触后性质 ,慢的长时程反应可能与多突触传递有关。灌流液中使用 5 0 μmol/LGABA可最大限度地降低听神经诱发的脑干神经元信号的幅度 ,BMI可部分逆转GABA对此信号的作用。 结论　 多部位的光学系统可以记录电刺激听神经的诱发反应 ,光学信号显示了时间 空间分布的类型。应用药理学的方法可以分析诱发反应的性质。GABA对出生后早期小鼠的诱发反应有明显的抑制作用 ,其抑制作用部分是通过GABAA受体实现的。     

γ-氨基丁酸对吗啡成瘾大鼠中枢神经系统痛觉的调制

目的 观察γ-氨基丁酸(γ-aminobutyric acid,GABA)对吗啡依赖大鼠中枢神经系统伏隔核(nucleus accumbens,NAc)痛兴奋神经元(pain-excited neurons,PEN)电活动的影响.方法 脑室或NAc中注射GABA或荷包牡丹碱(bicuculline,Bic),电脉冲刺激右侧坐骨神经作为伤害性疼痛刺激,用玻璃微电极在细胞外记录中枢神经系统伏隔核痛兴奋神经元电活动的变化.结果 脑室及NAc中注入GABA均能使吗啡依赖大鼠NAc中PEN潜伏期延长、痛诱发放电频率减少;GABAA受体拮抗剂Bic能够阻断GABA的上述效应.结论 外源性GABA在中枢痛觉调制中起抑制作用,GABA及GABAA受体参与介导中枢伤害性信息的传递过程.     

GABA对大鼠伏隔核痛反应神经元电活动的影响

目的在50只成年Wister大鼠上，观察了侧脑室(icv)注射GABA(γ-氨基丁酸)后，伏隔核(NAc)痛反应神经元放电的变化和荷包牡丹碱(Bic)对GABA作用的阻断效应，从而进一步研究GABA与NAc在痛觉调制中的作用。方法采用icy注射，电脉冲强直刺激坐骨神经作为伤害性痛刺激，玻璃微电极细胞外记录痛反应神经元放电的变化。结果(1)icv注入GABA能够使正常大鼠NAc中痛兴奋神经元(PEN)痛诱发放电频率减少、潜伏期延长，而使痛抑制神经元(PIN)痛诱发放电频率增加、诱发放电完全抑制时程缩短；(2)icv注入GABAA受体拮抗剂Bic能够阻断GABA的上述效应。结论(1)外源性GABA可使正常大鼠NAc中痛反应神经元对伤害性刺激的反应减弱，表现为镇痛效应；(2)GABA的这种镇痛作用主要是通过GABAA受体介导的。该结果揭示，GABA和NAc在痛觉调制中具有非常重要的作用。     

小脑表面刺激对猫癫痫模型痫样放电的影响及其机理的实验研究

在猫急性青霉素诱发的全身性癫痫模型上,小脑前叶刺激对脑电图上的痫样放电产生明显的抑制,而小脑半球表面刺激的抑制作用很弱。本实验还记录了小脑源性大脑皮层的诱发电活动,并从其与小脑表面刺激对痫样放电影响的关系上探讨小脑刺激抗痫作用机理。     

大鼠初级躯体感觉皮层后肢代表区的神经回路和时间可塑性:平面微电极阵列记录技术的应用(英文)

目的运用平面微电极阵列记录技术探讨大鼠初级躯体感觉皮层(primary somatosensory cortex,S1 area)后肢代表区的神经回路和时间可塑性。方法将急性分离的大鼠脑片置于MED-64系统的电极平皿中,持续灌流通入95%O2和5%CO2混合气的人工脑脊液,随后进行多电极同时同步记录。利用双线性内插法计算出64个点的电流源与电流井,并将其转换为二维电流源密度分布图。结果刺激S1后肢代表区脑片的II-III层,可鉴定出局部皮层内的连接回路,而刺激IV层(丘脑传入的主要终末端)则鉴定出丘脑皮层间的连接回路。首先,丘脑皮层投射的激活可以诱发更多的有效场电位,并且与S1区更多的神经元建立突触联系。与之相比,皮层内回路的激活引起的电反应活动范围则较小。其次,刺激IV层在每一刺激强度下诱发的场电位幅度远远大于刺激II-III的场电位幅度,即S1区更容易被丘脑皮层连接回路的投射纤维所激活。最后,在S1区IV层给予强直刺激可以记录到长达两个小时的局部场电位幅度的增加,长时程增强(long-term potentiation,LTP)的诱出率约为83.3%(5/6例)。相反,在II-III层,同样的强直刺激并...     

红核在大脑皮质下行调控脊髓伤害感受性传递中的作用

以电刺激外周感受野诱发的大鼠脊髓背角WDR和NS神经元的晚串放电（C-反应）为指标，以串脉中刺激对侧大脑脚（CP）作为条件刺激，在C-反应受到明显抑制的神经元。分别观察了电解损毁红核（RN）和RN内注射兴奋性氨基酸的受体拮抗剂对刺激CP的下行抑制作用的影响。结果发现：损毁同侧RN后，刺激CP对C反应的抑制作用明显减弱，而损毁同侧RN背侧结构，对侧RN及假损毁RN均无此效应；RN内微量注射兴奋性氨基酸受体拮抗剂AP5和DNQX均可减弱刺激CP对C-反应的抑制。提示RN至少部分参与大脑皮质对脊髓伤害感受性传递的下行抑制作用。且以同侧RN为主；在与痛觉调制有关的皮质-RN通路中既有NMDA受体又有非NMDA受体的参与。     

幼年大鼠大脑皮质5—HT1B受体中介的突触前抑制

5－HT灌流幼年大鼠脑片，66．7％额叶后部ⅣV层神经元由刺激丘脑后腹核引起的EPSPS或EPSCs出现抑制，膜电位和膜电阻无明显改变．此抑制作用为5－HT1B受体激动剂TFMPP和CGS—12066B模拟，被5—HT1A／1B受体拮抗剂pindolol阻抑，但不受其它5－HT亚型受体拮抗剂的影响，5－HT不降低低钙高镁液中外源性谷氨酸引致的去极化反应．上述结果提示，5－HT经突触前膜1B受体抑制神经元间的突触传递。     

去甲肾上腺素及拮抗剂、氟哌啶醇对大鼠海马CA_3区双脉冲反应的影响

目的 探讨脑诱发电位P_(50)感觉门控的神经学机制。方法 利用海马脑片技术,研究大鼠海马CA_3区双脉冲反应及药理特性。结果 双脉冲刺激苔藓纤维,可在海马CA_3区观察到长持续抑制(75～750ms),去甲肾上腺素(NE)(10μmol/L)减弱这种抑制。氟哌啶醇(50μmol/L)、酚妥拉明(75μmol/L)可阻断NE的去抑制作用,心得安(20μmol/L)则否,表明NE的去抑制作用与α受体有关。结论 海马CA_3区长持续抑制及药理特性与P_(50)感觉门控相似,提示这种抑制可能是P_(50)感觉门控的基础。     

大鼠三叉—小脑投射神经元表达磷酸激活的谷氨酰胺酶——双标法研究

磷酸激活的谷氨酰胺酶 (phosphateactivatedglutaminase,PAG)可作为谷氨酸能神经元的标志物。采用逆行束路追踪技术和PAG免疫荧光组织化学法 ,研究脑干三叉核团复合体中向小脑袢状小叶Crus1区投射神经元是否呈PAG样免疫反应阳性。结果表明 :将荧光金 (Fluoro Gold ,FG)注入小脑袢状小叶Crus1区后 ,在三叉神经感觉主核 (Pr5 )、三叉神经脊束核极间亚核 (Sp5I)和吻侧亚核背内侧部 (Sp5DM)、三叉间核 (I5 )以及三叉神经运动核与上橄榄核之间的一个小区域 (nucleusJ)中均可见到FG逆行标记细胞。标记细胞出现在上述核团的双侧 ,但以同侧为主。PAG免疫荧光组织化学反应结果显示 :许多FG标记神经元呈强PAG样免疫阳性 ,其中FG/PAG双标神经元占FG逆行标记神经元总数的 73%～ 94 %。结果提示 :脑干三叉神经核团中的谷氨酸能神经元可能参与触觉信息从面口部向小脑的传递。     

大鼠三联单叉神经中脑核内囊泡膜谷氨酸转运体样和GAD样阳性末梢与GABAA受体α1亚单位样阳性神经元的联系

最近已在哺乳类动物脑内克隆出两种新的脑内特殊的Na+依赖的无机磷酸转运体,它们均属于囊泡膜谷氨酸转运体,被分别命名为VGluTl(Vesicular glutamate transporter of type1)和DNPI(differentiation-associatedNa+-dependent inorganicphosphate eotransporter).本研究应用免疫荧光组织化学三重染色技术,在激光共聚焦显微镜下观察了大鼠三叉神经中脑核(Vine)内VGIuT1样和DNPI样以及谷氨酸脱羧酶(GAD)样阳性末梢与GABAA受体α1亚单位(GABAARa1)样阳性神经元之间的联系.结果显示:①几乎所有的Vme神经元均呈GABAA受体α1亚单位样免疫阳性,吻尾方向在其全长出现,这些神经元绝大多数为大的假单极神经元(直径为25～50um),但也有小部分为直径小于25um的神经元.②大量的VGluT1样和DNPI样免疫阳性的神经纤维和末梢广泛分布于Vine内,其中DNPI样阳性纤维和末梢的分布密度高于VGIuT1;同时还观察到GAD样阳性纤维和末梢也密集分布于Vme内.③VGluT1样、DNPI样和GAD样免疫阳性终扣分别包绕在GABAA受体α1亚单位样阳性Vine神经元胞体周围,并与之形成密切接触.以上结果提示:Vme神经元在介导面口部本体感觉信息的传递中,可能同时接受中枢其他来源的谷氨酸能和GABA能末梢的调控,其中GABA能的投射末梢可能通过位于Vine神经元内的GABAA受体对面口部本体感觉信息的传递发挥抑制性调控作用.     

Neuroimaging in epilepsy in tropics

Epilepsy is a major public health problem in many tropical countries. Also, some of the tropical diseases are major contributors to the higher prevalence of epilepsy in these countries. The etiologic factors responsible for epilepsy in these countries are quite different from those in the developed world. This article discusses the etiologic factors and neuroimaging of epilepsy in light of the conditions in these tropical countries.     

癫痫与抑郁关系的研究进展

抑郁是癫痫患者中常见的精神障碍,严重地影响了患者的生活质量。传统的观点认为癫痫患者因为存在着诸多社会学问题易出现抑郁倾向,癫痫和抑郁是单向的联系,但大量的研究已经证明癫痫和抑郁之间存在双向的联系,一种异常状态的存在可能易转化为另一种异常状态的发展。癫痫和抑郁存在着共同的发病机制。本文主要就癫痫和抑郁的双向联系以及抗抑郁药物在癫痫患者中的应用进行阐述。     

Sudanophilic lipid accumulation in astrocytes in periventricular leukomalacia in monkeys

Summary Sudanophilic lipid accumulation is a characteristic feature of periventricular leukomalacia (PVL) of infants. At least two types of lipid-containing cells have been identified, one being the macrophage, the other the pre-myelin glial cell. A third type of lipid-containing cell has been seen in two monkeys with spontaneous PVL. Electron microscopically this cell appears to be an astrocyte. This probably represents a reaction of the astrocyte to hypoxia and may be the equivalent of the hypertrophic astrocytes found in human infants.Supported in part by NIH grant HDO 8633 and the Regional Primate Research Center Grant RR-00166     

Increase in cathepsin D activity in rat brain in aging

Cathepsin D-like activity in homogenates of five brain areas of 3-month-old and 24-month-old Fischer 344 rats was measured. With hemoglobin as substrate at pH 3.2, more than 90% of the activity was inhibited by pepstatin. In each area studied, activity was more than twice as high in the old rat brain: 140-160% higher in the cortex, cerebellum, pons-medulla, and striatum and 90-100% higher in the hippocampus and spinal cord. The greatly increased metabolic capacity in the absence of an increase in protein turnover may have a role in age-related pathological degeneration in the brain.     

Gender in Voice Perception in Autism

Deficits in the perception of social stimuli may contribute to the characteristic impairments in social interaction in high functioning autism (HFA). Although the cortical processing of voice is abnormal in HFA, it is unclear whether this gives rise to impairments in the perception of voice gender. About 20 children with HFA and 20 matched controls were presented with voice fragments that were parametrically morphed in gender. No differences were found in the perception of gender between the two groups of participants, but response times differed significantly. The results suggest that the perception of voice gender is not impaired in HFA, which is consistent with behavioral findings of an unimpaired voice-based identification of age and identity by individuals with autism. The differences in response times suggest that individuals with HFA use different perceptual approaches from those used by typically developing individuals.     

Increase in noradrenaline-synthesizing enzyme activity in medulla oblongata in Parkinson's disease

Summary Dopamine beta hydroxylase (DBH), the noradrenaline-synthesizing enzyme, and phenylethanolamine-N-methyltransferase (PNMT), the adrenaline-synthesizing enzyme, were assayed in 18 areas of brain stem in eight cases of parkinsonian syndromes and of four age- and postmortem delay-matched controls. Dissection was performed by the punch technique and enzyme activities assayed by radiometric methods. No significant change was found for PNMT activity. DBH activity was significantly increased in the A2-C2 area of the medulla oblongata (including the nucleus tractus solitarius) in the cases of Parkinson's disease.The A2-C2 area is known to be implicated in the control of blood pressure in rats. These findings are discussed in relation to orthostatic hypotension and the influence ofl-dopa therapy.Supported by grants from INSERM ATP 657897, ATP 8179113, CRL 79-1-356-6, DGRST (80 E 0882), FRMF, and Sandoz-France France     

Changes in parasympathetic system in medulla oblongata in male pigs in the course of tachycardia-induced cardiomyopathy

Background

Autonomic imbalance constituting a fundamental feature of heart failure (HF) has been assessed mainly at the periphery. Changes in the functioning of autonomic centers in the brain remain unclear. We investigated the molecular elements of parasympathetic system, i.e. α7 nicotinic acetylcholine receptor (α7nAChR) and enzymes metabolizing acetylcholine (acetylcholinesterase, AChE, choline acetyltransferase, ChAT) in medulla oblongata (MO) of male pigs with chronic tachycardia-induced cardiomyopathy.

Methods

The mRNA levels of AChE, ChAT, α7nAChR and X-box binding protein 1 (spliced form, XBP1s) in MO were analyzed using qPCR, AChE and ChAT activities using spectrophotometry, proteasome activity using fluorometry, and the protein level of α7nAChR using Western blotting.

Results

The development of systolic HF was accompanied by an increase in circulating catecholamines, a decrease in the AChE and α7nAChR mRNA in MO, an increase in AChE activity (all p < 0.05), and no change in either the mRNA or activity of ChAT. Both circulating catecholamine levels and AChE activity were inversely related to systolic function of left myocardial ventricle (p < 0.05). The level of α7nAChR protein in MO and its cytoplasmatic fraction were higher in pigs with moderate and severe HF as compared to the other animals (p < 0.01). There was no difference in proteasome activity in MO between diseased and healthy animals, whereas the XBP1s mRNA decreased during HF progression (p < 0.05).

Conclusions

Molecular elements of parasympathetic system are changed within the medulla oblongata during the progression of systolic non-ischemic heart failure in male pigs, indicating a functional link between MO and heart in HF.     

Issues in evaluation of cognition in the elderly in developing countries

Background:

Developing regions of the world host the majority of elderly subjects who are at risk for dementia. Reliable epidemiological data from these countries is invaluable in tackling this global problem. Scarcity of such data in literature is largely attributable to problems that are unique to developing communities worldwide.

Objective:

To classify and describe the problems that interfere with the collection of reliable epidemiological data on cognitive impairment in the elderly in developing communities, and to suggest practical solutions for some of them.

Methods:

Inferring from the experiences of a large, ongoing, population-based study on the cognitive impairments in the elderly in South India and from the review of literature.

Conclusion:

A fatalistic attitude regarding aging in the communities, significant heterogeneity in educational abilities and activities of daily living, high illiteracy among rural subjects, and lack of an organized health care system and updated demographic figures are some of the major factors that contribute to technical, namely, methodology-related problems and practical, namely, subject-related problems in such epidemiological studies.     

Characteristics of nociceptors in the periodontium--an in vitro study in rats

Recent studies have indicated that nociceptors can be classified into various types according to their physiological properties. These studies have clarified that the frequency distribution of various nociceptor types is different among body sites and animal species. In the present study, we investigated the physiological properties of rat's periodontal nociceptors in an in vitro jaw-nerve preparation. Responses were recorded from functional single filaments in the inferior alveolar nerve. To determine the nociceptor type, calibrated von Frey filaments, heat, and bradykinin (BK) stimuli were used. We found five subtypes of nociceptors in the periodontal ligaments of the lower incisor: Adelta-high threshold mechanonociceptors (Adelta-HTM, n=28), Adelta-mechanoheat nociceptors (Adelta-MH, n=6), Adelta-polymodal nociceptors (Adelta-POLY, n=26), C-high threshold mechanonociceptors (C-HTM, n=3) and C-polymodal nociceptors (C-POLY, n=4). Most nociceptors were Adelta-innervated, while only a small number of C-innervated nociceptors were found. The present results suggest that periodontal nociceptors transmit mainly fast pain, and may thus play a role in rapid detection of injure-related stimuli during mastication.     

Suicide in the elderly in Austria

In most countries men and women have the highest suicide rates in age groups over 60 years. We investigated suicide rates for the elderly in Austria, a country with one of the highest suicide rates in the world, for the period 1980–1991, using data from the Federal Statistical Division. Suicide rates remained stable over the last decade at a very high level. The mean rate for men was 85.2, for women 28.6/100 000. In men and women rates rise with age. The mean rate of men rises from 51.2 (60–64 years) to 117.3/100 000 (over 85 years); in women there is an increase from 21.4 (60–64 years) to 32.8/100 000 (over 85 years). We did not confirm findings in other countries, where suicide rates have increased in recent years.