大麻素治疗精神障碍的研究进展

大麻素作为大麻的主要活性成分,是大麻中特有的一组具有复杂活性的萜类次生代谢产物.自发现大麻素能够治疗某些精神障碍以来,揭示大麻素治疗精神障碍的药用机制逐渐成为相关领域热点科学问题.然而,截至目前,仍然只有较少证据支持任何一种大麻素成分的药用疗效和安全性.目前,关于大麻素治疗精神障碍相关的基础和临床研究层出不穷,学界对大...     

内源性大麻素系统和突触可塑性研究进展

突触可塑性是学习和记忆的神经基础,随着近些年对内源性大麻素系统研究的深入,内源性大麻素作为逆向信号分子在突触信号传递中发挥调节作用引起了重视。内源性大麻素系统介导的突触可塑性分为短期可塑性和长期可塑性,介导的短期可塑性又可分为:去极化介导的、受体介导的、Ca2+协助受体介导的、突触激发介导的四种内源性大麻素释放方式。内源性大麻素系统还参与神经胶质细胞和神经细胞粘附分子对突触可塑性的调节。现就内源性大麻素系统在调节突触可塑性生理机制的研究进展做一综述。     

大麻素与疼痛

多年来一直有种说法:与大麻类似或由其衍生称为大麻素(cannabinoid)的物质,能够止痛.不过,其主要依据都是来自逸闻,而且即使所言属实,究竟大麻素是直接缓解疼痛,还是它另外的行为性或欣快作用的结果?仍然是个谜.现在,细致的研究表明大麻素可直接干扰神经系统的疼痛信号,这个深刻认识可能引出一类新的止痛药. 青铜币标示了公元315到392的年份;正在分娩的年轻女子的骷髅,还有一堆灰色碳化了的物质,这些是耶路撒冷附近一个古墓的出土文物.研究人员怀疑大约1600年以前,那个女子使用那种灰色物质来缓解分娩的疼痛.那么这种神秘的粉末究竟是什么呢?研究人员称,那是大麻的残留物.     

精神分裂症患者颞上回的大麻素受体密度没有显著性变化

目的 近年来研究发现,在精神分裂症患者的内源性大麻素递质系统会出现异常变化,而颞上回在精神分裂症的病理生理机制中和幻听症状密切相关.因此,对照正常人群,我们研究了精神分裂症患者颞上回大麻素CB-1受体的密度变化.方法 采用定量放射自显影技术,通过[3H]SR141716A(CB-1受体选择性拮抗剂)和[3H]CP-55940(CB-1受体激动剂)检测颞上回CB-1受体密度水平.死后脑组织由澳大利亚新南威尔士州组织资源中心提供.结果 先前研究发现,精神分裂症患者与认知功能失常相关的额前叶,前、后扣带回皮质的CB-1受体密度水平有异常改变.与此相反,本研究发现在精神分裂症患者的由[3H]SR141716A和[3H]CP-55940检测的颞上回大麻素受体密度水平和对照组比较没有显著变化.结论 我们认为颞上回大麻素CB-1受体和精神分裂症患者的发病及幻听症状无关.     

大麻素系统与帕金森病及其运动并发症关系的研究进展

近来研究显示，非多巴胺代偿机制在帕金森病及其运动并发症的发展过程中起着重要作用，大麻素系统即其中热点之一，尤其是大麻素CB1受体在运动活动的调节枢纽基底节中具有大量分布。本文对大麻素CB1系统在帕金森病及左旋多巴诱导异动症中作用的研究进展进行阐述，同时简要分析了其作用机制。     

内源性神经保护因子花生四烯酰多巴胺的研究进展

正哺乳动物体内存在内源性大麻素系统,该系统包括内源性大麻素、大麻素受体以及合成、运输和降解它们的酶。花生四烯酰多巴胺(N-arachidonoy ldopamine,NADA)是一种重要的内源性大麻素,在抗氧化、抗炎、免疫调节、抗兴奋毒性和调节突触可塑性等方面发挥着重要的神经保护作用,可作为神经退行性疾病治疗的新靶点。本研究就目前有关NADA、NADA受体及其病理生理功能进行综述,以期为中枢神经系统疾病的治疗提供新的思路。1 花生四烯酰     

大麻素与多发性硬化(综述)

人体内存在CB1和CB2两种大麻素受体亚型,大麻素类药物主要作用于该受体途径,可缓解多发性硬化所致的肌肉痉挛、震颤、疼痛等症状,并通过抑制神经兴奋毒性及对免疫系统的调节作用起到神经保护作用。     

内源性大麻素与精神障碍

内源性大麻素系统是中枢神经系统内重要的调控系统,可调节认知、情绪、行为等,被认为与精神分裂症、抑郁障碍、精神活性物质所致精神障碍等密切相关。对内源性大麻素系统的深入研究旨在为精神障碍的治疗提供新的思路。     

精神分裂症与内源性大麻素系统关系的研究进展

精神分裂症是一种复杂的精神疾病,表现为思维、情感、认知、行为等方面的异常。内源 性大麻素系统是一种内源性生物信号系统,在精神分裂症发病中发挥着重要作用。现就精神分裂症中 内源性大麻素系统的改变进行综述。     

精神分裂症与内源性大麻素系统关系的研究进展

精神分裂症是一种复杂的精神疾病，表现为思维、情感、认知、行为等方面的异常。内源 性大麻素系统是一种内源性生物信号系统，在精神分裂症发病中发挥着重要作用。现就精神分裂症中 内源性大麻素系统的改变进行综述。     

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.