脑源性神经营养因子在抑郁症中的研究进展

脑源性神经营养因子（brain-derived neurotrophic factor,BDNF）是参与机体情绪和认知功能至关重要的调节因子,能够促进脑内神经发生和突触发育。在抑郁患者及抑郁动物模型中,BDNF前体（brain-derived neurotrophic factor precursor,proBDNF）和前肽水平升高,BDNF成熟体（mature brain-derived neurotrophic factor,mBDNF）水平降低;抗抑郁药物治疗后,能够抑制proBDNF以及BDNF前肽的表达,促进mBDNF/proBDNF蛋白比值的升高。目前临床常见抗抑郁药的抗抑郁作用多依赖于BDNF及相关蛋白的信号转导。本文通过查阅文献,对BDNF及其相关因子在抑郁症中的作用进行总结。     

脑源性神经营养因子的研究进展

近年来,科学研究发现神经营养因子是参与调控神经系统多种生理功能的一种蛋白质。其中,脑源性神经营养因子是一种在脑内合成的小分子二聚体蛋白质,对中枢系统神经元的生长、发育、分化、再生和修复具有重要作用。本文对脑源性神经营养因子的结构、功能、疾病相关性及临床应用前景进行了综述。     

脑源性晕厥的病因分析

目的探讨脑源性晕厥的病因。方法对186例晕厥患者进行各项实验室检查。特别是应用影像学检查方法。分析其基础疾病,实验室检查结果,分析26例诊断为脑源性晕厥患者的病因。结果26例患者均检出有不同程度的血管病变及颅内病变。无明显的致晕厥的心脏疾患。均可诊断为脑源性晕厥。结论部分晕厥为脑源性晕厥,对不明原因的晕厥患者除了行常规的实验室检查外,要给予血管影像学检查。     

脑源性神经营养因子与脑缺血的研究进展

脑源性神经营养因子(brain derived neurotrophic factor,BDNF)是在脑内形成的一类神经营养因子。BDNF通过作用于其特异性受体TrkB、P75促进神经元的生长发育同时修复受损的神经元。BDNF对缺血性脑损伤的保护机制是通过下调钙离子浓度,减小Bax/Bcl-2比值,对抗NO毒性等途径实现的。该文介绍了BDNF的基本作用及其与脑缺血的相关作用研究,综述了BDNF的应用方法研究。     

脑源性神经营养因子与抑郁症关系的研究进展

神经营养因子(neurotrophin,NT)是一类能促进神经细胞生长、发育和分化的多肽或蛋白质,能调节神经元存活,激活酶的活性,阻止成年神经元损伤后的死亡,具有促进神经元损伤后的修复以及轴突再生,调节突触可塑性和神经递质等功能[1].     

脑源性神经营养因子与中枢神经损伤

<正>脑源性神经营养因子(Brain-derived neurotrophie factor,BDNF)由Barde等于1982年首次从猪脑提取液中获得,是相对分子质量为1213kD的碱性蛋白,为神经营养素家族成员之一,广泛分布于中枢神经系统(Central nervous system,CNS)。目前国内外已经对BDNF的生物学作用进行了广泛的研究,证实它不仅在中枢神经系统发育过程中对神经元的生存、分化、生长和维持神经元正常的生理功能起     

脑源性神经营养因子前体的研究进展

神经营养因子是一种分泌性多肽类生长因子家族,参与神经系统的多种生理功能活动,研究发现成熟的脑源性神经营养因子与其前体分子具有不同的生物学活性,它们的受体以及介导的细胞内信号通路也大相径庭。本文对近年来关于脑源性神经营养因子前体分子的研究进展予以综述,着重讨论其体内分布、生物合成与分泌、生物学活性以及与疾病的联系。研究脑源性神经营养因子前体分子在生理和病理状态下的作用将对未来的药物开发和神经系统疾病的治疗具有重要的意义。     

脑源性神经营养因子在抑郁症发生和治疗中的研究进展

目前临床常用的抗抑郁药主要通过增加脑内突触间隙单胺类递质的浓度、增强单胺类神经的功能而起效,但这一机制不能很好地解释抗抑郁药存在的起效时间长等现象.近年提出,抗抑郁药可能还通过增加海马区域脑源性神经营养因子(BDNF)基因表达起效.抗抑郁药能增加受试动物海马区BDNF基因表达,抑郁患者接受抗抑郁药治疗,其血清BDNF水平上升;BDNF基因的单核苷酸多态性也与抑郁症的发生有关;抗抑郁药可能还通过激活丝裂原活化蛋白激酶(MAPK)信号通路,磷酸化cAMP反应序列结合(cREB)蛋白,最终使BDNF基因表达上调.这一机制的提出为抑郁症生物学病因的阐明提供了必要信息,同时也有助于抗抑郁新药的开发,为研制安全、有效的新药提供新的思路.     

甲基苯丙胺成瘾者戒断期的脑源性神经营养因子变化研究进展

脑源性神经营养因子(brain-derived neurotrophic factor,BDNF)参与了神经发生、神经可塑性及认知功能等多种神经活动,参与学习和记忆的过程,对神经可塑性的调节和损伤后修复具有重要影响,被认为是与成瘾行为相关的生物标志物.本文回顾了国内外BDNF与物质成瘾关系以及甲基苯丙胺成瘾者戒断期外周...     

不同时间脑室注射脑源性神经营养因子治疗新生大鼠缺氧缺血性脑损伤效果的比较

目的　比较新生大鼠缺氧缺血性脑损伤后不同时间脑室注射脑源性神经营养因子 (BDNF)对脑损伤的影响。方法　 7d龄SD大鼠左侧颈总动脉结扎后行 8%低氧吸入 2 5h形成缺氧缺血性脑损伤 ,伤后 0、1和 4h分别向脑室注射0 5 μgBDNF ,观察对脑水肿、皮层和海马脂质过氧化物(MDA)水平和细胞凋亡的影响。结果　伤后即刻给予BD NF减轻脑水肿、防止MDA过量产生和细胞凋亡增加的效果最为显著 ,伤后 4h给予效果较差。结论　BDNF对新生大鼠缺氧缺血性脑损伤后的皮层和海马具有显著的保护作用 ,以早期应用效果较为明显     

Transport of brain-derived neurotrophic factor across the blood–brain barrier

Brain-derived neurotrophic factor (BDNF) is a potential therapeutic agent for degenerative disorders of the central nervous system. In this report, we investigated the ability of BDNF to cross the blood–brain barrier (BBB). BDNF was stable in blood up to 60 min after i.v. injection, with evidence for aggregation, and had an early, rapid influx into brain. By 10 min, most of the BDNF sequestered by the cerebral cortex was associated with the parenchyma rather than with the endothelial cells, demonstrating complete passage across the BBB. A small dose of unlabeled BDNF enhanced the entry of ¹²⁵I-BDNF from blood to brain after an i.v. bolus injection, whereas larger doses had no effect. In contrast, a large dose of unlabeled BDNF inhibited the influx of ¹²⁵I-BDNF during in situ brain perfusion. After intracerebroventricular injection, the efflux of BDNF from brain to blood occurred at a rate similar to that for reabsorption of cerebrospinal fluid, and no evidence for self-inhibition was found. Therefore, we conclude that intact BDNF in the peripheral circulation crosses the BBB by a high-capacity, saturable transport system.     

柴胡皂苷a抗抑郁作用机制的研究进展

抑郁症是一种常见的精神类疾病,发病率高、致死率高,严重影响人类身体健康。柴胡具有疏肝解郁之功效,临床上多用其复方制剂治疗抑郁症。近年来发现,柴胡中的柴胡皂苷a具有潜在的抗抑郁作用,能通过调节炎症因子及相关通路,增强神经营养因子表达,改善神经递质水平及神经元细胞凋亡,下调下丘脑-垂体-肾上腺（HPA）轴功能发挥抗抑郁作用。主要对柴胡皂苷a的抗抑郁作用机制进行综述,便于为药物研发和抑郁症的研究提供思路。     

慢性应激与去睾丸减少成年小鼠脑中NT-3和BDNF的蛋白表达(英文)

研究了慢性应激对小鼠脑中神经营养因子蛋白表达的影响 ,并探讨了性激素降低是否参与此过程 .性成熟完整雄性小鼠和去睾丸小鼠接受慢性应激 6 0d ,完整动物海马和大脑皮层中神经营养因子3(NT 3)和脑源性神经营养因子 (BDNF)蛋白水平显著降低 ,而且NT 3在海马齿状回的降低呈现某种程度的特异性 ,此外 ,齿状回颗粒细胞的形态退化在整个脑中也最为明显 ;去睾丸应激动物海马和大脑皮层中BDNF和NT 3蛋白水平较完整动物进一步降低 ,尤其是海马齿状回NT 3蛋白水平的降低与其他脑区相比表现出明显的特异性 ,同样 ,慢性应激引起的大脑皮层和海马特别是齿状回的神经元退化进一步被去睾丸恶化 .结果表明 ,慢性应激可抑制脑中NT 3和BDNF蛋白表达 ,去睾丸可使这种变化进一步加剧 ,海马齿状回对应激神经毒性较为敏感 ,提示 :脑中BDNF和NT 3蛋白水平降低与慢性应激过程中大脑形态退化密切相关 ;性激素降低在应激诱导的大脑退化过程中可能扮演着重要角色     

Effects of venlafaxine given repeatedly on α1‐adrenergic,dopaminergic and serotonergic receptors in rat brain

Venlafaxine (VEN), a representative of a new class of antidepressants (serotonin and noradrenaline reuptake inhibitors, SNRI), administered repeatedly affects—as was demonstrated by us previously—the behavioural responsiveness of α₁‐adrenergic, dopaminergic (D₂ and D₃) and serotonergic systems to their agonists. In the present study we aimed to find out whether parallel changes in the binding to the respective receptors also occurred. The experiment was carried out on male Wistar rats. VEN was administered in a dose of 10 mg/kg once or repeatedly (14 days, twice daily). The obtained results showed that VEN did not change the binding (B_max and K_D) of α₁‐adrenergic receptors to [³H]‐prazosin in the cerebral cortex, having increased only its displacement by phenylephrine. The binding (B_max and K_D) to D₁ and D₂ receptors in the limbic forebrain and the striatum was not affected by repeated venlafaxine when [³H];‐SCH 23390 and [³H]‐spiperone, respectively, were used as ligands. When [³H]‐quinpirole was used as a ligand, the binding was enhanced in the striatum, the nucleus accumbens (shell and core) and islands of Calleja. VEN also increased the binding of [³H]‐7‐OH‐DPAT to D₃ receptors in islands of Calleja and the nucleus accumbens (shell). In the serotonergic system, a decrease in the density of 5‐HT_1A receptors was observed in the hippocampus, whereas no changes occurred in the binding of 5‐HT₂ receptors in the cortex. Thus VEN given repeatedly enhanced the binding (of the ligands that are agonists) to dopamine D₂ and D₃ receptors. Weaker effects were observed in the α₁‐adrenergic and the serotonergic systems. Copyright © 1999 John Wiley & Sons, Ltd.     

Effects of interleukins 2 and 12 on TBT-induced alterations of MAP kinases p38 and p44/42 in human natural killer cells

NK cells are lymphocytes in the non-adaptive immune system that protect the body against intracellular pathogens and eliminate tumor cells. Tributyltin (TBT) is a toxic chemical that has been detected in human foods as well as in human blood. The role of TBT in immunosuppression has been described, including inhibition of the human NK-cell cytotoxic function. Previous studies indicated that exposure of NK cells to TBT for 1 h induced progressive and irreversible inhibition of cytotoxic function. However, it was found that if NK cells were incubated in TBT-free media with either IL-2 or IL-12, loss of cytotoxic function was prevented/reversed within 24 h. Molecular studies established that loss of cytotoxic function is accompanied by alteration of MAP kinases (MAPKs) p38 and p44/42 phosphorylation. This study examined whether interleukin-mediated recovery of cytotoxicity involved reversal of tributyltin-altered p38 and p44/42 phosphorylation. The results indicated that there was no substantial IL-2 prevention/reversal of the TBT-induced alteration of phosphorylation of either p38 or p44/42 after either a 24 or 48 h recovery period. Additionally, IL-12 caused no substantial prevention/reversal of the TBT-induced alteration of phosphorylation of the MAPKs seen after either 24 or 48 h. These data suggest that IL-2 and/or IL-12-mediated recovery of NK cytotoxic function is not a result of prevention/reversal of TBT-induced phosphorylation of p38 and p44/42 MAPKs at the 24 or 48 h time points.     

Effect of risperidone on plasma catecholamine metabolites and brain-derived neurotrophic factor in patients with bipolar disorders

A combination treatment with a mood stabilizer and an antipsychotic drug is often used in as many as 90% of subjects with acute mania. Recently, augmentation therapy with atypical antipsychotics has been investigated in both the acute and long-term treatment of bipolar disorder with or without psychosis. In the present study, the authors investigated the efficacy of risperidone treatment for both acute manic and depressive episodes in bipolar disorder. Eighteen patients (M/F: 8/10, age: 34 +/- 15 yr) who met the DSM-IV criteria for bipolar I disorder (12 cases of manic episodes, 6 cases of depressive episodes) with risperidone treatment were evaluated regarding their clinical improvement using the Young Mania rating Scale (YMRS) and the Hamilton rating Scale for Depression (Ham-D). Plasma concentrations of HVA and MHPG were analyzed by HPLC-ECD and plasma brain-derived neurotrophic factor (BDNF) levels were detected by sandwich ELISA. The mean scores of the YMRS were 22, 18, 12, 8, and 5 at time points before and 1, 2, 3, and 4 weeks after the risperidone administration, respectively. The mean scores of the Ham-D were 24, 25, 21, 21, and 19 at time points before and 1, 2, 3, and 4 weeks after the risperidone administration, respectively. The plasma levels of HVA and 3-methoxy-4-hydroxyphenylglycol (MHPG) were observed to have decreased 4 weeks after risperidone administration in manic patients. The levels did not change in depressive patients. The plasma levels of BDNF were decreased in depressive patients compared with manic patients or healthy controls. However, the administration of risperidone did not alter plasma BDNF levels.     

脑源性生长因子参与疼痛-抑郁共病的研究进展

疼痛和抑郁症存在共病联系,两者之间可能存在共同的神经解剖机制及分子机制。近年来研究发现,中枢神经系统中的脑源性生长因子(brain-derived neurotrophic factor,BDNF)在疼痛-抑郁共病过程中发挥重要作用,BDNF也逐渐成为疼痛及抑郁症的研究热点及治疗靶点。该文就BDNF参与疼痛-抑郁共病的机制及外周血BDNF在疼痛、抑郁症的诊治中的意义做论述。