抑郁症患者中升高的前列腺素E1与抑郁样行为相关

目的研究在抑郁症(MDD)患者队列外周血及慢性不可预知温和型应激(CUMS)小鼠模型大脑组织中前列腺素E1(PGE1)浓度及其代谢通路上的关键基因(PLA2、PTGS1、PTGS2和PTGES)表达量的改变,以明确PGE1的改变与MDD疾病间的关系。方法用高效液相色谱(HPLC)检测受试者外周血浆和CUMS小鼠脑组织中PGE1和PGE2的浓度;用RT-qPCR检测PLA2、PTGS1、PTGS2和PTGES的mRNA表达水平。结果在MDD患者中,血浆PGE1浓度和PTGS1的表达水平均显著上升(P0.05)。这一结果在CUMS小鼠外周血和大脑杏仁核组织中得到了有效验证。结论 PGE1在MDD中的上升,可能与前列腺素合成通路的功能亢进有关。     

γ-氨基丁酸与精神分裂症的分子遗传学研究进展

精神分裂症是一种全球性的疾病,其终生患病率约为1%…,不仅给患者本人及家属带来极大的痛苦,而且也给整个社会带来沉重的经济负担.翟金国等[2]调查发现精神分裂症患者年人均总花费约为1.65万元,远高于我国人均年收入水平.γ-氨基丁酸(γ-aminobutyric,GABA)是哺乳动物中枢神经系统中主要的抑制性神经递质,广泛存在于大脑各区,与注意、工作记忆、情绪、运动抑制等多种脑高级功能有关,如前额叶的GABA不足影响注意和抑制功能,易产生冲动性行为.近年来一些有关精神分裂症的基础神经科学研究与临床研究及动物模型研究均发现精神分裂症有GABA神经递质系统的改变,而这些改变可能就是精神分裂症的发病机制之一[3].笔者将对精神分裂症有关GABA受体及转运体分子遗传学等方面的研究进展做一综述.     

平阳霉素治疗淋巴管瘤的临床疗效分析

淋巴管瘤多见于儿童 ,其中囊状淋巴管瘤尤多见于 2岁以下者 ,以往对此病的治疗主要选择外科手术切除 ,但效果不太理想。 Yura等人提出用Bleomycin(博莱霉素 )治疗淋巴管瘤和囊状水瘤 ,获得了较好的效果。近年 ,我科用平阳霉素治疗了 1 7例 ,也获得了良好的效果。特报道于下。1　临床资料与治疗方法本组收集 1 7例病例 ,男女比例为 9∶ 8,最小年龄 8个月 ,最大年龄 2 9岁 ,中位年龄段为 2～ 8岁。发病部位 :囊状淋巴管瘤好发颈部 ,共 5例 :海绵型淋巴管瘤好发于颌面各个部位 ,其中颊部 3例、颌下2例、额部 2例、舌部 4例。注射次数因肿瘤类…     

毛细管电泳技术在疾病基因诊断方面的应用

近年来分子生物学和遗传学的迅速发展,使人们对基因结构与功能的认识日益加深。科学工作者们发现基因的某些突变可导致疾病的发生或易感性增加。因此可以通过对疾病相关基因的分析进行疾病诊断或预告;对于那些尚未确定致病基因的遗传病也可利用DNA标记进行遗传连锁分析?..     

Hijacking Dorsal Raphe to Improve Moods and Metabolism via BDNF Gene Transfer in Mice

Background: Mood disorders such as depression and metabolic diseases like obesity and diabetes have significant comorbidities; furthermore, each disease increases the risk of the other one. Continuing use of antidepressant medication is associated with an elevated risk of type 2 diabetes and weight gain. On the other hand, antiobesity drugs are found to have varying neuropsychiatric adverse event profiles. Therefore, there is an urgent need to develop more effective and safer therapies for mood disorders and metabolic diseases with minimal side effects. Both brain derived neurotrophic factor (BDNF) and serotonin (5-HT) can regulate moods in the limbic system and metabolism in the hypothalamus, respectively. The dorsal raphe nucleus (DR) in the midbrain contains the largest number of serotonin-expressing neurons as well as other neurons expressing various neurotransmitters. Both serotonergic and nonserotonergic DR neurons send projections widely to the forebrain including the limbic system and the hypothalamus. This study aimed to investigate whether BDNF gene transfer in DR neurons can improve moods and metabolism. Methods: Recombinant adeno-associated virus (AAV) was microinjected into DR to achieve BDNF gene transfer. Chronic unpredictable mild stress (CUMS) model of depression in C57BL/6 mice was established to investigate the role of DR BDNF gene transfer in depression. Forced swimming test (FST) and sucrose consumption test (SCT) were used to examine the depressive-like behaviors. Open field test (OPT) and elevated zero maze (EZM) were used to examine the anxiety-like behaviors. Diet-induced obesity (DIO) and leptin receptor mutant db/db mice were employed to investigate the role of DR BDNF gene transfer in regulating metabolism. Metabolic profiling included body weight, food intake, fat mass, serum factors, energy expenditure, glucose tolerance and insulin sensitivity. Quantitative RT-PCR was performed to determine expression changes of several key genes in DR, hypothalamus, liver and fat tissues. Tph2 conditional knockout mice were used to examine whether 5-HT is essential for BDNF in improving metabolism. In addition, chemogenetic activation of DR neurons via AAV-mediated hM3Dq expression was also performed to examine whether there is a similar effect as BDNF. Results: FST and SCT showed significant anti-depressant effects of DR BDNF gene transfer in the CUMS model, meanwhile, OPT and EZM showed significant anxiolytic effects. BDNF gene transfer in DR also markedly ameliorated obesity and hyperglycemia in DIO and db/db mice, which was revealed by lightened body weight, decreased food intake, increased energy expenditure, improved glucose tolerance and insulin sensitivity, reduced levels of serum factors like insulin and leptin. The mRNA expression of genes related to 5-HT signaling such as tph2 and vmat2 was significantly increased in DR after BDNF gene transfer. Expression levels of multiple genes regulating energy balance in the hypothalamus, liver, and fat tissues also changed. Conditional knockout of tph2, encoding the rate-limiting enzyme of 5-HT synthesis, did not block the effects of DR BDNF gene transfer in improving metabolism. Chemogenetic activation of DR neurons also had the effects of improving metabolism in DIO mice. Conclusions: BDNF gene transfer in DR of mice improves moods and metabolism. This study surmounts the “hypothalamocentric” paradigm dominating in metabolism research by connecting metabolism and moods via dorsal raphe.     

两种体外培养星形胶质细胞的比较

目的 对2种常用培养方法得到的星形胶质细胞进行生物学功能上的比较分析。方法 用啮齿类新生儿大脑星形胶质细胞分离培养方法培养原代星形胶质细胞,用胎牛血清分化神经干细胞制备分化星形胶质细胞。显微镜下观察2种星形胶质细胞的细胞形态并用免疫荧光染色检测星形胶质细胞特异性标志物胶质纤维酸性蛋白(GFAP)的表达量,10种细胞因子处理2种细胞后检测GFAP等的变化,用表达谱芯片检测GFAP、谷氨酸合成酶(GS)、转运蛋白(xCT)、神经调节蛋白-1(NRG)、谷氨酸受体蛋白(NMDA)、脂蛋白脂肪酶(LPL)等基因的表达并进行比较。结果 2种星形胶质细胞形态和GFAP表达量不同,表达谱芯片检测结果显示原代星形胶质细胞GFAP、GS、xCT、NRG、NMDA、LPL基因的表达均显著高于分化星形胶质细胞。10种细胞因子的处理均不能使原代星形胶质细胞GFAP表达升高,但转化生长因子-β(TGF-β)可以使分化的星形胶质细胞GFAP表达升高。结论 与分化的星形胶质细胞相比,原代培养的星形胶质细胞更类似于反应态星形胶质细胞,而TGF-β可促进分化细胞向反应态细胞过渡。     

精神分裂症遗传易感性研究进展

精神分裂症是人类最常见的精神疾患之一，属于复杂的多基因遗传性疾病。随着分子生物学技术和遗传学数据分析方法的进步，精神分裂症易感基因方面的研究也取得了一定的进展。本文就近年来国际上关于精神分裂症遗传易感性研究的一些成果进行综述，主要内容包括：(1)精神分裂症分子遗传学研究的基本策略与方法；(2)精神分裂症易感基因的全基因组扫描研究结果；(3)依据精神分裂症发病的三大假说，进行的候选基因研究的部分结果；(4)采用新型多位点联合作用分析方法，寻找精神分裂症的易感基因。     

Schizophrenia susceptibility genes on chromosome 13q32

Schizophrenia is a complex mental disorder affecting approximately 1% of the general population worldwide.1 It has a high incidence in the general population, a poor prognosis and a poor outcome, in that it has become a major social problem. Family, twin, and adoption studies have clearly shown that a genetic component is quite likely to play an important role in determining susceptibility to schizophrenia. The genome-wide scan indicates that several chromosomal regions are linked to schizophrenia, some of which have been replicated independently including 6p21-24, 8p21-22, 13q14-33 and 22q11-12.2,3 This study was designed to detect two single nucleotide polymorphisms (SNPs) located in the 13q14-33 region, rs188608 at the STK24 locus and rs2892679 at the GPC6 locus, among Chinese population.     

血糖控制对初诊2型糖尿病患者胰岛β细胞功能的影响

目的:探讨短期持续皮下胰岛素输注(CSII)治疗对初诊2型糖尿病(T2DM)患者的降糖效果和胰岛β细胞功能的影响。方法:对30例初诊T2DM患者进行为期2周的CSII强化治疗,分析比较治疗前后空腹(FPG)及餐后2h血糖(2hPG)、静脉葡萄糖耐量试验时第一时相胰岛素及C肽分泌、△I30/△G30和由Homa模型计算的Homaβ、HomaIR。结果:CSII强化治疗显示出快速稳定的降血糖效果。葡萄糖刺激后第一时相胰岛素和C肽的分泌、△I30/△G30和Homaβ均较治疗前明显升高(P<0.01)。HomaIR较治疗前明显下降(P<0.01)。结论:短期CSII强化治疗可显著改善初诊T2DM患者胰岛β细胞功能。