P2X7受体在中枢神经系统中的作用研究进展

P2X7受体是ATP敏感的离子通道受体的一种,其在中枢神经系统(CNS)表达丰富。目前研究证明,P2X7受体不但在CNS生理过程中发挥重要作用,而且参与多种CNS疾病的病理过程。了解P2X7受体在CNS主要的生理机制和病理过程,阐明P2X7受体治疗方案在CNS相关疾病中的运用具有重要意义。现就P2X7受体在CNS中的作用研究进展进行综述。     

P2X受体在中枢神经系统中的表达及功能

腺嘌呤核苷酸受体（P2受体）的概念于1978年提出，这类受体包括配体门控离子通道受体P2X和G蛋白耦联受体P2Y两个家族。迄今为止，已有七个亚型的P2X受体（P2X1,7）和八个亚型的P2Y受体（P2Y1,2,4,6,11,12,13,14）被克隆。其中P2X受体家族被认为是继烟碱受体家族及谷氨酸受体家族后第三类配体门控的离子通道。随着研究的不断深入，目前已经明确P2X受体广泛存在于中枢神经系统（CNS）并执行多种生理功能。[第一段]     

P2Y受体与神经变性病

嘌呤能P2受体家族分为离子通道P2X受体和G蛋白偶联的促代谢型P2Y受体。P2Y受体包括P2Y1、P2Y2、P2Y4、P2Y6、P2Y11、P2Y12、P2Y13及P2Y14,其在神经系统广泛分布,在神经元存活及神经炎性因素中起着重要作用。本文对P2Y受体的分类、分子结构特征,神经系统分布以及在神经变性病中所起的作用做一综述。     

多巴胺D4受体基因及其与精神分裂症的关系

多巴胺功能亢进是解释精神分裂症病因机制的主要生化假说。近年来发现,多巴胺D4受体在精神分裂症病因发病中起着重要的作用,编码D4受体的基因与精神分裂症间可能也有着重要的联系。一、关于多巴胺D4受体根据多巴胺受体对腺耷酸环化酶（AC）活性的不同影响,多巴胺受体可分为多巴胺D1类受体和D2类受体,D1类受体可激活AC的活性,D2类受体则抑制或不影响AC的活性。由于这两类受体对不同的多巴胺受体激动剂、拈抗剂的选择性及亲合力不同,D1类受体又可分成D1受体和D5受体,D2类受体则可分成D2、D3和D4受体。1．D4受体的结构特征：D4…     

低剂量左旋多巴对帕金森病大鼠纹状体乙酰胆碱M1和M2受体表达的影响

目的探讨低剂量的左旋多巴对帕金森病(PD)大鼠纹状体乙酰胆碱M1、M2受体表达的影响。方法将成功建模的20只PD大鼠随机分为模型对照组、左旋多巴干预7d、14d、21d组(每组5只),另将5只正常大鼠设为空白对照组。采用免疫组化技术测定纹状体乙酰胆碱M1和M2受体的表达情况。结果 M1受体蛋白在帕金森病大鼠中的表达高于空白对照组,药物干预7d、14d后M1受体蛋白表达较模型对照组明显降低(P0.05),但在药物干预21d后M1受体蛋白表达明显回升(P0.05);M2受体蛋白表达在帕金森病大鼠模型对照组较空白对照组明显下降(P0.05),但在用药物进行干预后较空白对照组无明显回升(P0.05)。结论帕金森病大鼠在低剂量的左旋多巴干预后M1受体蛋白的表达是一个动态变化变化过程,而M2受体蛋白的表达在药物干预后较空白对照组无明显变化。     

抑郁症和去甲肾上腺素能受体

去甲肾上腺素(NE)能受体分为α_1、α_2和β受体,α_2受体在前突触被激动时,NE释放减少,降低后突触β受体的激活,使抑郁加重。α_1受体被激动则出现精神运动性激活。反复激动β受体,致低敏和向下调节,起着抗抑郁作用。     

人巨细胞病毒感染对人脑血管平滑肌细胞AT受体基因表达的影响

目的:探讨血管紧张素受体1、2(AT1,AT2)及人巨细胞病毒(HCMV)感染在动脉粥样硬化过程中的作用。方法:建立HCMV感染细胞模型,采用RT-PCR等技术研究在更昔洛韦(GCV)和AT1、AT2受体拮抗剂作用下,HCMV对体外培养人脑动脉血管平滑肌细胞AT1和AT2受体基因表达的影响。结果:HCMV感染体外培养的人脑血管平滑肌细胞上调了AT1和AT2受体的基因表达,AT1和AT2受体拮抗剂及GCV能够抑制HCMV感染对人脑血管平滑肌AT1和AT2受体的激活作用。结论:HCMV感染引起人脑血管平滑肌细胞增生可能由于AT1和AT2受体基因表达的激活。     

杏仁核毁损对甲基苯丙胺精神分裂症大鼠边缘区多巴胺D2受体的影响

目的探讨立体定向杏仁核毁损对甲基苯丙胺(methamphetamine,MAP)精神分裂症大鼠脑内边缘区多巴胺D2受体表达的影响.方法40只SD大鼠随机分为对照组、模型组、假手术组和手术组,每组各10只;采用经腹腔注射MAP制备精神分裂症MAP模型,立体定向-射频毁损杏仁核,原位杂交法观察边缘区多巴胺D2受体的表达.结果与对照组比较,模型组及假手术组大鼠边缘区多巴胺D2受体表达有非常显著性差异(P＜0.01);手术组大鼠边缘区多巴胺DA受体阳性细胞数目与对照组比较差异无显著性(P＜0.01).结论杏仁核毁损可以抑制使用MAP而诱发的边缘区D2表达的亢进.     

去甲肾上腺素的临床效应

去甲肾上腺素（NE）能激动α和β受体，其中俚受体又分为α1和α2受体，本文将介绍激动这些受体的临床效应。     

大鼠脊髓内5-HT2C,5-HT3,5-HT6和5-HT7受体亚型mRNAs的表达

目的:观察5-HT2C,5-HT3,5-HT6和5-HT7受体亚型mRNAs在大鼠脊髓不同节段的表达.方法:反转录PCR方法.结果:5-HT2C受体亚型mRNA在颈、胸、腰、骶段脊髓的背角(DH)和前角(VH)均有较强的表达;5-HT3受体mRNA在各节段脊髓DH的表达水平较高,而在VH则较低;与5-HT3受体亚型相反,5-HT6受体亚型mR-NA在脊髓VH的表达水平高于DH;5-HT7受体mRNA在脊髓的表达则与5-HT3受体相似,在各节段的DH均有较高水平的表达.不同的受体亚型在脊髓同一节段以及同一受体亚型在不同脊髓节段的表达水平存在差异.结论:本研究结果表明,上述四种5-HT受体亚型在脊髓具有不同的表达特点,提示它们在脊髓水平可能发挥着不同的生理作用,并为深入探讨5-HT受体参与伤害性感受和运动的调节机制提供了依据.     

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.     

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.     

Defects in Bioenergetic Coupling in Schizophrenia

Synaptic neurotransmission relies on maintenance of the synapse and meeting the energy demands of neurons. Defects in excitatory and inhibitory synapses have been implicated in schizophrenia, likely contributing to positive and negative symptoms as well as impaired cognition. Recently, accumulating evidence has suggested that bioenergetic systems, important in both synaptic function and cognition, are abnormal in psychiatric illnesses such as schizophrenia. Animal models of synaptic dysfunction demonstrated endophenotypes of schizophrenia as well as bioenergetic abnormalities. We report findings on the bioenergetic interplay of astrocytes and neurons and discuss how dysregulation of these pathways may contribute to the pathogenesis of schizophrenia, highlighting metabolic systems as important therapeutic targets.     

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.     

Ethnic disparities in problem behaviour in adolescence contribute to ethnic disparities in social class in adulthood

BACKGROUND: It is important for prevention of social class disparities to know how ethnic disparities in social class arise among migrant children. We contribute to this understanding by examining the role of problem behaviour in adolescence. METHODS: Prospective observational study with 753 Dutch native and 217 Turkish migrant adolescents (11-18 year) followed for 10 years. Internalising and externalising problems were assessed in adolescence and employment status and occupational level were assessed in adulthood. The difference in odds ratios (OR) before and after adjustment for internalising and externalising problems was an indication of the predictive value of disparities in internalising and externalising problems for the development of social class disparities. RESULTS: A total of 135 (62%) of the Turkish and 602 (80%) of the Dutch adults were employed. Internalising and externalising problems were not associated with employment status. Of the employed, 65 (48%) Turkish and 179 (30%) Dutch adults worked in low-level occupations (p < 0.0001). Internalising and externalising problems were associated with both ethnicity and occupation. The OR for low-level occupation for Turkish adults was 1.78 (1.19-2.65), indicating ethnic disparities. Adjustment for internalising problems lowered the OR with 36% to 1.50 (0.97-2.31), and adjustment for externalising problems lowered it with 8% to 1.72 (1.15-2.57). Findings were similar for men and women and did not vary by age. CONCLUSIONS: Ethnic disparities in occupational level in adulthood could partly be attributed to disparities in mental health between Turkish migrants and Dutch natives in adolescence. Prevention of ethnic disparities in mental health at young age may therefore also contribute to the prevention of occupational differences in adulthood.     

Progress in neuroprotection in Parkinson's disease

Slowing or aborting the progress of neurodegeneration in Parkinson's disease (PD) remains the most important unmet need of this disorder. There are several recent developments in trial design and also in drugs under investigation for possible neuroprotective effect. Emphasis has been placed on clinical as opposed to imaging end-points and these include change in a clinical rating scale, e.g. United Parkinson's disease Rating Scale (UPDRS), or time to additional therapy. The introduction of the delayed-start, or wash-in, trial design adds an additional dimension to drug evaluation for neuroprotection. Compounds that have been recently tested in clinical trial include the monoamine oxidase-B inhibitor rasagiline, the anti-apoptotic agents TCH346 and CEP1347, and the promitochondrial agent creatine. The dopamine agonists have been evaluated for a neuroprotective effect using imaging end-points. Perhaps the most important and simplest concept for neuroprotection has been the theory that early dopaminergic support for the degenerating dopaminergic system per se provides significant long-term clinical benefit for PD patients.     

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.