脑源性神经营养因子与抑郁症

脑源性神经营养因子(brain-derived neurotrophic factor,BDNF)是神经营养家族中的重要成员。BDNF可促进神经系统的发育,维持神经系统的功能,在各种神经的生长发育以及再生中起重要作用。近年来的研究表明,BDNF在抑郁症及其并发症的诊治中发挥重要作用。该文综述了BDNF、BDNF受体和信号转导通路在抑郁症以及糖尿病、脑卒中、产后、慢性疼痛等并发抑郁症中的研究现状。     

脑源性神经营养因子与脑卒中后疼痛和抑郁的关系

脑源性神经营养因子（BDNF）是成人脑内含量最丰富的神经营养因子,具有显著的脑损伤修复能力。最近的多项研究表明,BNDF在脑卒中后的多种并发症的发生发展中起到了重要的作用,有希望成为新的卒中治疗方法的晚期靶点,但它的作用机制尚不明确。本文就BDNF的生物学特性、在卒中后并发症的作用机制以及最新的研究进展进行综述,从而为...     

脑源性神经营养因子在实验性糖尿病及其并发症中的表达及研究

脑源性神经营养因子（BDNF）属于一类神经营养因子,与对应受体TrkB相结合充分发挥有效生理作用能够促进神经系统发育、分化、生长,并促使神经元保持正常生理功能,与糖尿病存在较为密切相关性。本文分析BDNF与糖尿病及并发症相关性进行综述研究。     

锂对中枢神经和血液系统的作用（二）

许多学者报道抑郁使得脑内脑源性神经营养因子（BDNF）减少，锂通过增加脑内的BDNF而发挥作用。锂和丙戊酸盐选择性地激活神经元内脑源性神经营养因子促进因子Ⅳ，提高海马内BDNF的水平。锂和匹鲁卡品诱导的癫痫持续状态与大鼠脑BDNF广泛增高有关。锂也能增加大鼠海马内的神经生长因子（NGF），但丙戊酸和安非他命都不改变脑内的NGF。     

脑源性神经营养因子与脑卒中后疼痛和抑郁的关系

脑源性神经营养因子(BDNF)是成人脑内含量最丰富的神经营养因子, 具有显著的脑损伤修复能力。最近的多项研究表明, BNDF在脑卒中后的多种并发症的发生发展中起到了重要的作用, 有希望成为新的卒中治疗方法的晚期靶点, 但它的作用机制尚不明确。本文就BDNF的生物学特性、在卒中后并发症的作用机制以及最新的研究进展进行综述, 从而为脑卒中后疼痛及抑郁的临床诊治提供一种新的思路。     

脑源性神经营养因子与缺血性损伤

脑源性神经营养因子是神经营养因子(NTFS)中的一种，其在神经元损伤后再生修复和防止神经细胞退行性变等方面发挥了重要作用。许多研究表明，BDNF对限制脑缺血后分解代谢产物所产生的损伤级联反应有重要作用。本就其可能的作用机制及未来前景展望作一综述。     

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。     

神经生长因子和脑源性神经营养因子对神经干细胞迁移的影响

目的:探讨神经生长因子(nervegrowth factor,NGF)与脑源性神经营养因子(brain-derived neurotrophic factor,BDNF)体外实验对神经干细胞迁移的影响.方法:体外应用半固体培养法连续14d观察不同浓度的NGF、BDNF及NGF +BDNF组合诱导神经干细胞迁移的情况.结果:体外条件下不同浓度的神经营养因子的组间和组内比较显示,100μg/L BDNF诱导神经干细胞迁移作用最明显.BDNF+NGF联合组在诱导神经干细胞迁移方面未见协同效应.结论:NGF、BDNF二者皆有诱导神经干细胞迁移的作用,100μ g/L BDNF组诱导迁移作用最明显.     

脑源性神经营养因子对离子通道的调节作用

脑源性神经营养因子（brain derived neurotrophic factor,BDNF）是神经营养因子（neurotrophicfactors,NTF）家族成员之一,对中枢和周围神经系统多种神经元的生长、发育、分化、维持和损伤修复起重要作用。BDNF还能够调节神经元静息膜电位、神经兴奋性和突触传递,在突触可塑性过程中起重要作用,这些作用与其对离子通道的调节有关。BDNF不仅可以与TrkB受体结合激活第二信使级联反应和蛋白磷酸化过程调节离子通道的性质,还可以直接调节钠通道活性。可见,BDNF还具有神经调质和兴奋性递质的作用。     

脑源性神经营养因子在炎症性肠病中的作用

脑源性神经营养因子（brain-derived neurotrophic factor,BDNF）是神经营养因子（neurotrophin,NT）家族中的重要成员,在神经元的维持和存活,保持突触完整性和突触可塑性中起重要作用,但其作用不仅限于此。研究发现BDNF在炎症性肠病（inflammatory bowel disease,IBD）中具有维持内脏超敏反应,促进肠道动力,维持肠道屏障,调节情绪障碍及心脏功能的作用,可能在IBD的发生发展中起重要作用。虽然目前大多限于基础研究,但已经取得了一定的成果,可以预见BDNF将有很好的临床应用前景,可能为IBD的临床治疗提供新的治疗思路。对此,本文作一简要综述。     

BDNF and NT-3 but not CNTF counteract the Ca2+ ionophore-induced apoptosis of cultured cortical neurons: involvement of dual pathways

The effect of neurotrophic factors on apoptosis induced by ionomycin, a potent Ca2+ ionophore, was investigated using cultured cortical neurons from embryonic rats. Brain-derived neurotophic factor (BDNF) and neurotrophin-3 (NT-3) prevented the ionomycin-mediated cell death in a dose-dependent manner. In contrast to the neurotrophins, cilliary neurotrophic factor (CNTF) did not rescue neurons from cell death induced by ionomycin. The protective effect of BDNF was partially blocked by wortmannin, a phosphatidylinositol 3-kinase inhibitor, and by PD98059, a MAP kinase kinase inhibitor. However, the addition of both compounds together completely inhibited the survival promoting effect of BDNF. These results suggest that the neuroprotective effect of BDNF requires activation of both phosphatidylinositol-3 kinase and the Ras/MAP kinase cascade and that CNTF signaling through other pathways is without an effect in this system.     

Neurotrophic factors--a tool for therapeutic strategies in neurological, neuropsychiatric and neuroimmunological diseases?

Nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) belong to the protein family of neurotrophins. They both display profound neuromodulatory functions and are essentially involved in the survival and homeostatic maintenance of central and peripheral neurons during development and adulthood. Moreover, NGF and BDNF are known to modulate immune cell function and thus serve as mediators in the reciprocal cross talk between neurons and immune cells. Neurotrophic factors have been implicated in pathophysiological mechanisms of many diseases of the nervous and the immune system, such as amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD), neuropathy, pain, allergic bronchial asthma (BA) and neurotrophic keratitis. For all these diseases research has reached the point of creating strategies for therapeutic intervention with neurotrophins. In this review, we present an overview of the pathophysiology, therapeutic interventions and strategies concerning NGF and BDNF in the mentioned diseases.     

Exogenous gangliosides increase the release of brain-derived neurotrophic factor

Gangliosides are lipophilic compounds found in cell plasma membranes throughout the brain that play a role in neuronal plasticity and regeneration. Indeed, absence or abnormal accumulation of gangliosides has been shown to lead to neurological disorders. Experimental data have shown that exogenous gangliosides exhibit properties similar to the neurotrophins, a family of neurotrophic factors that are important in the survival and maintenance of neurons and prevention of neurological diseases. Brain-derived neurotrophic factor (BDNF) is the most abundant of the neurotrophins. This work was done to reveal the neurotrophic mechanism of exogenous gangliosides. In particular, we examined whether gangliosides promote the release of BDNF. Rat hippocampal neurons or human neuroblastoma cells were transduced with a recombinant adenovirus expressing BDNF-flag to facilitate detection of BDNF. Release of BDNF was then determined by Western blot analysis and a two-site immunoassay of culture medium. The depolarizing agent KCl was used as a comparison. In hippocampal neurons, both GM1 ganglioside and KCl evoked within minutes the release of mature BDNF. In human cells, GM1 and other gangliosides released both mature BDNF and pro-BDNF. The effect of gangliosides was structure-dependent. In fact, GT1b preferentially released mature BDNF whereas GM1 released both mature and pro-BDNF. Ceramide and sphingosine did not modify the release of BDNF. This work provides additional experimental evidence that exogenous gangliosides can be used to enhance the neurotrophic factor environment and promote neuronal survival in neurological diseases. This article is part of a Special Issue entitled 'Trends in neuropharmacology: in memory of Erminio Costa'.     

穴位埋线与VD模型大鼠记忆障碍及其海马BDNF表达的关系

目的探讨穴位埋线对血管性痴呆(VD)大鼠记忆障碍的改善及与脑源性神经生长因子(BDNF)的关系。方法采用改良Pulsinelli’s四血管阻断法建立血管性痴呆大鼠模型,造模后给予穴位埋线治疗。用水迷宫检测学习记忆能力;HE染色法观察海马齿状回神经元形态变化;免疫组化观察海马BDNF的表达。结果穴位埋线后VD大鼠学习记忆能力明显提高;海马齿状回神经元损伤减少、BDNF的表达增强。结论穴位埋线治疗后VD大鼠的学习记忆能力提高,可能与它增强海马BDNF的表达和保护海马神经元有关。     

Plasticity of central monoaminergic systems during aging]

The locus coeruleus (LC), located within the caudal pontine central gray, is composed of noradrenaline-containing neurons. The axons of these neurons form extensive collateral branches that project widely to many brain sites. The function of the LC is still unclear at present, however, LC neurons are known to exhibit marked axonal regeneration and sprouting in response to brain damage. We investigated the age-related changes in noradrenergic innervations of the frontal cortex, using in vivo electrophysiological techniques and immunohistochemistry. While noradrenergic innervations gradually decreased with age in the frontal cortex, a high degree of sprouting occurred in the LC axon terminals in middle age. Neither the electrophysiological properties of LC neurons nor NA levels in the frontal cortex changed with age. These findings suggested that the LC neurons preserve a strong capacity to remodel their axon terminals even in the aging brain. Exogenous brain-derived neurotrophic factor (BDNF) infusion caused a marked increase in the density of noradrenergic axon in the aged brain, but no trophic action of BDNF was observed in the young or middle-aged brain. The result suggests that BDNF is necessary for the maintenance of noradrenergic innervations in the aged brain.     

Brain derived neurotrophic factor and neurodegeneration

Brain derived neurotrophic factor (BDNF) was the subject of over one hundred patents in the past three years. The majority of these patents propose new methods to increase its bioavailability and clinical benefit (that is yet to be defined in the adult human nervous system). The major limitation in the current neurotrophic factor (NTF) research, impairing relevant comparisons of preclinical results, is the incomplete methodological standardisation in measuring the effects of BDNF in experimental models. Nevertheless, BDNF has clearly emerged as the leading candidate to become the pluripotent neurotrophic factor that may soon be either the prime factor or at least a universal adjuvant in future neuroregenerative therapies. Furthermore, our current understanding of BDNF receptor biology, especially of the high affinity tyrosine kinase B (trkB) receptor, has spurred research targeting the design of more potent BDNF-like synthetic ligands. Finally, new strategies are currently explored to increase the target availability of BDNF and expand its biological life.     

普拉克索和罗匹尼罗对体外培养的多巴胺神经元的神经营养作用

目的 :探讨新型选择性多巴胺D3受体激动剂普拉克索和罗匹尼罗对多巴胺神经元的神经营养作用及其机制。方法 :在大鼠的腹侧中脑细胞和不同部位星形胶质细胞培养基中加入普拉克索和罗匹尼罗刺激 ,观察药物对多巴胺神经元存活的影响。结果 :药物直接作用或从黑质区星形胶质细胞培养基中提取的条件培养液均可使酪氨酸羟化酶 (TH )阳性神经元数量增加 ,同时培养液中脑源性神经营养因子 (BDNF)和胶质细胞源性神经营养因子(GDNF)含量增加。而其他脑区的星形胶质细胞不能产生类似作用。结论 :普拉克索和罗匹尼罗对多巴胺神经元具有神经营养作用 ,这可能是由于其使特定区域星形胶质细胞产生并分泌了神经营养因子。     

Family-based study of brain-derived neurotrophic factor (BDNF) gene polymorphism in alcohol dependence

Brain-derived neurotrophic factor (BDNF) belongs to a family of proteins related to the nerve growth factor family, which are responsible for the proliferation, survival and differentiation of neurons. BDNF is thought to be involved in the pathogenesis of bipolar disorder, schizophrenia, eating disorders and addiction. We hypothesize that a functionally relevant polymorphism of the BDNF gene promoter may be associated with the pathogenesis of alcohol dependence. We performed an association study of 141 families with alcohol dependence. One hundred and thirty-eight healthy control subjects were matched based on ethnicity and gender. An association between the BDNF Val66Met gene polymorphism and alcoholism was not found.     

BDNF在局部脑缺血大鼠的表达

目的 观察大鼠脑缺血后脑源性神营养因子(BDNF)含量的变化.方法 用大鼠大脑中动脉线栓法(MCAO)建立脑缺血模型,免疫组织化学观察BDNF在不同时间点表达变化.结果 与假手术组比较,脑缺血模型组大鼠BDNF在MCAO后缺血6 h表达增强(P＞0.05),48 h达高峰(P＜0.05).结论 脑缺血后神经元内BDNF含量增多,可有利丁受损神经元的修复.