脑源性神经营养因子研究现状

本文主要综述了脑源性神经营养因子（ｂｒａｉｎ－ｄｅｒｉｖｅｄｎｅｕｒｏｔｒｏｐｈｉｃｆａｃｔｏｒ，ＢＤＮＦ）的发现、生化特性、与神经生长因子（ＮＧＦ）和神经营养因子Ⅱ（ＮＴ－３）属于同一基因家族以及靶源性等概念：总结了脑源性神经营养因子对运动神经元、胆碱能神经元、多巴胺神经元及感觉等其它神经元的效应作用，并展望了应用脑源性神经营养因子治疗运动神经元病变及老年神经系统退行性疾病的前景。     

脑源性神经营养因子研究现状

近年来神经科学的研究表明,神经营养因子是选择性调节周围神经和中枢神经系统神经生长和存活的一类蛋白质。脑源性神经营养因子（brain derived neurotrophic factor,BDNF）是神经生长因子（nerve growth fac-tor,NGF)发现后约30年由德国神经生物学家Barde^[1]报告的另一神经营养因子,它对CNS多种类型神经元的生长、发育、分化、维持和损伤修复都具有重要作用,对神经系统疾病诸如早老性痴呆、帕金森氏病和肌萎缩侧索硬化等退变性疾病的治疗具有潜在应用前景。本文就脑源性神经营养因子的结构、功能及应用前景作一综述。     

脑源性神经营养因子的研究现状

自50年代，Levi－Montalcini首次从雄性小鼠颌下腺中分离出神经生长因子（neruegrowthfactor，NGF）[1]以来，对它的研究一直在神经生物学中占据着重要地位，已证明它能调节许多神经元的重要功能。1982年，Barde等人从猪脑中分离纯化得到脑源性神经营养因子（brain－derivedneu     

脑源性神经营养因子对学习和记忆作用的研究进展

脑源性神经营养因子(BDNF)在中枢神经系统中生物学效应非常广泛,本文探讨了BDNF通过胆碱能神经系统、海马LTP以及小脑等方面对学习和记忆所产生的作用,总结了近年来的研究进展.     

脑源性神经营养因子与癫痫

癫痫发作可诱导海马内脑源性神经营养因子(BDNF)水平上调,进而激活海马门区及CA3区腔隙层的TrkB受体,通过促进兴奋性神经递质释放等效应加强海马通路尤其是苔状纤维的兴奋性突触传递,从而导致持续的高度兴奋状态;而阻断BDNF信号转导通路则可抑制癫痫发生.提示BDNF在癫痫发作过程中具有重要作用,进一步阐明其细胞分子机制将为探索癫痫治疗手段提供新途径.     

Notch-1对嗅成鞘细胞脑源性神经营养因子表达的影响

目的:观察Notch-1对嗅成鞘细胞(OECs)脑源性神经营养因子(BDNF)表达的影响,为增强OECs对中枢神经系统损伤的修复能力提供实验基础.方法:将有活性的Notch质粒(NotchICV),无活性的Notch质粒(NotchVK)以及空白质粒转入OECs中,将实验对象分成活性质粒组、非活性质粒组和空白组,通过免疫荧光双标、RT-PCR及免疫印迹技术检测各组OECs中BDNF的表达变化.结果:活性质粒组OECs中BDNF及其mRNA的表达较非活性质粒组和空白组均增高,而非活性质粒组和空白组比较无差异.结论:Notch-1转染OECs后,其BDNF的表达上调,提示Notch-1能增强OECs中BDNF的合成.     

脑源性神经营养因子与帕金森病

帕金森病 (PD)的最主要病理特征是中脑黑质致密部(substantia nigra pars com pacta,SNpc)多巴胺 (DA)能神经元的进行性退化变性 ,由于其机制还不清楚 ,因而限制了此病的临床治疗。脑源性神经营养因子 (brain- derived neu-rotrophic factor,BDNF)由 Barde等于 1982年在猪脑中首次发现 ,其氨基酸序列有 5 5 %～ 6 0 %与神经生长因子 (nervegrowth factor,NGF)完全相同 ,也属神经营养素 (neu-rotrophin)家族的成员 ,BDNF可通过其高亲和力受体 trk B和低亲和力受体 p75 NTR发挥生物活性 ,能够促进多种神经元的存活 ,尤其对 DA能神经…     

脑源性神经营养因子与缺血性脑血管病的研究进展

脑源性神经营养因子（BDNF）为神经营养因子（NTFs）中的一种，是1982年Barde及其同事从猪脑提取液中获得的分子量为12．3KD①的碱性蛋白质，有119个氨基酸组成，含有3对二硫键，等电点为10左右。研究表明BDNF是一种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极其重要作用的细胞因子。近年来神经细胞培养和动物实验研究表明，     

Role of brain-derived neurotrophic factor in Huntington's disease

Neurotrophic factors are essential contributors to the survival of peripheral and central nervous system (CNS) neurons, and demonstration of their reduced availability in diseased brains indicates that they play a role in various neurological disorders. This paper will concentrate on the role of brain-derived neurotrophic factor (BDNF) in the survival and activity of the neurons that die in Huntington's disease (HD) by reviewing the evidence indicating that it involves profound changes in BDNF levels and that attempts to restore these levels are therapeutically interesting.

BDNF is a small dimeric protein that is widely expressed in adult mammalian brain and has been shown to promote the survival of all major neuronal types affected in Alzheimer's disease (AD) and Parkinson's disease (PD). Furthermore, cortical BDNF production is required for the correct activity of the corticostriatal synapse and the survival of the GABA-ergic medium-sized spiny striatal neurons that die in HD. We will highlight the available data concerning changes in BDNF levels in HD cells, mice and human postmortem samples, describe the molecular evidence underlying this alteration, and review the data concerning the impact of the experimental manipulation of BDNF levels on HD progression. Such studies have revealed a major loss of BDNF protein in the striatum of HD patients which may contribute to the clinical manifestations of the disease. They have also opened up a molecular window into the underlying pathogenic mechanism and new therapeutic perspectives by raising the possibility that one of the mechanisms triggering the reduction in BDNF in HD may also affect the activity of many other neuronal proteins.     

Polymorphisms of brain-derived neurotrophic factor associated with heroin dependence

Brain-derived neurotrophic factor (BDNF) promotes synaptic remodeling and modulates the function of other neurotransmitters. It also plays a role in the reward response to many drugs, including heroin. To identify genetic variants associated with heroin dependence, we compared four single nucleotide polymorphisms (SNPs, rs13306221, rs6265, rs56164415, and rs16917204) of the BDNF gene in 487 subjects with heroin dependence and 492 healthy individuals. The analysis revealed the G allele of rs6265 was significantly more common in heroin-dependent subjects than in the healthy controls (P=0.001 after Bonferroni correction). Among heroin-dependent individuals, the onset of dependence was significantly earlier in individuals with GG or GA genotypes compared to AA individuals (P<0.01). Additionally, we found that the G allele of rs13306221 was significantly more frequent in heroin-dependent subjects than in controls (P=0.005 after Bonferroni correction). These findings support a role of BDNF rs6265 and rs13306221 polymorphisms in heroin dependence and may guide future studies to identify other genetic risk factors for heroin dependence.     

Influence of exercise on serum brain-derived neurotrophic factor concentrations in healthy human subjects

The effect of short-term exercise (15 min step-exercise) on serum brain-derived neurotrophic factor (BDNF) levels was evaluated in healthy human subjects. Results showed a short-term, significant increase in serum BDNF levels after exercise. Intra-individual differences in serum BDNF levels were remarkably small on the rest day and also when compared to rest values on the day of the exercise test. Inter-individual differences, on the other hand, were larger by comparison. The result of this study supports the need for larger sample size in studies on BDNF changes in psychiatric disorders or psychiatric drug effects.     

Decreased serum brain-derived neurotrophic factor levels in schizophrenic patients with tardive dyskinesia

The pathogenesis of tardive dyskinesia (TD) may involve neurodegeneration and associated dysfunction of brain-derived neurotrophic factor (BDNF) for the survival and maintenance of function in neurons. We therefore compared serum BDNF levels in schizophrenic patients with (n = 129) and without TD (n = 235), and normal controls (n = 323). Assessments included the abnormal involuntary movement scale (AIMS) and the positive and negative syndrome scale (PANSS). Our results were that patients with TD had lower serum BDNF levels than those without TD and normals. Lower serum BDNF levels were correlated with greater PANSS negative subscores, but not correlated with the AIMS scores. Serum BDNF levels did not differ between patients on typical and atypical antipsychotics and were not correlated with antipsychotic doses or years of exposure. We concluded that decreased BDNF levels might be associated with TD pathophysiology and more negative symptoms of schizophrenia.     

Serum levels of brain-derived neurotrophic factor in patients with schizophrenia and bipolar disorder

There is evidence that major psychiatric discords such as schizophrenia (SZ) and bipolar disorder (BD) are associated with dysregulation of synaptic plasticity with downstream alterations of neurotrophins. Brain-derived neurotrophic factor (BDNF) is the most widely distributed neurotrophin in the central nervous system (CNS), and performs many biological functions such as promoting the survival, differentiation, and plasticity of neurons. Variants in the BDNF gene increase the risk of SZ and bipolar disorder. Chronic administration of drugs used to treat SZ and BD, such as lithium, valproate, quetiapine, clozapine, and olanzapine, increases BDNF expression in rat brain. To examine serum BDNF, three groups of chronically medicated DSM-IV SZ patients, on treatment with clozapine (n = 27), typical (n = 14), and other atypical antipsychotics (n = 19), 30 euthymic BD patients, and 26 healthy control had 5 ml blood samples collected by venipuncture. Serum BDNF levels were significantly higher in SZ patients (p < 0.001) when compared to either controls or euthymic BD patients. Increased BDNF in SZ patients might be related to the course of illness or to treatment variables. Prospective studies are warranted.     

Physiological variability in brain-derived neurotrophic factor expression predicts dendritic spine density in the mouse dentate gyrus

Dendritic spines are the predominant sites of excitatory neurotransmission in the adult brain, and brain-derived neurotrophic factor (BDNF) is a well-characterized determinant of dendritic spine number and morphology. The relationship between BDNF expression and dendritic spine number is particularly evident in the hippocampus, where environmental conditions that enhance hippocampal BDNF levels also promote local increases in dendritic spine density. However, the relationship between physiological variability in hippocampal BDNF expression and spine number has yet to be assessed. To determine whether natural variability in BDNF expression is associated with hippocampal dendritic spine number, correlations between BDNF protein levels and dendritic spine density among Golgi-impregnated neurons in the hippocampal dentate gyrus and CA1 subfields were assessed in adult male C57Bl/6J mice. In the dentate gyrus, but not in the apical oblique dendrites of CA1 pyramidal cells, BDNF protein expression was significantly correlated with dendritic spine density. This observation suggests that there may be a subregionally specific relationship between hippocampal BDNF expression and the density of spines.     

脑源性神经营养因子Val66Met基因多态性与首发精神分裂症临床特征的关联研究

目的 探讨脑源性神经营养因子(brain-derived neurotrophic factor,BDNF)基因Val66Met多态性与首发精神分裂症临床特征的关联性.方法 应用TaqMan荧光探针技术对135例首发精神分裂症患者及483名正常对照者进行基因分型;采用阳性与阴性症状量表(positive and negative syndrome scale,PANSS)评估精神分裂症患者临床特征.结果 精神分裂症患者组与正常对照组BDNF Val66Met基因型及等位基因分布频率的差异具有统计学意义(P＜0.01);Met/Met基因型患者的PANSS总分、焦虑(抑郁)因子分及认知损害因子分均高于Val/Val和Val/Met基因型患者,差异有统计学意义(P＜0.01).结论 BDNF基因Val66Met多态性可能与精神分裂症的发病有关;首发精神分裂症患者中Met/Met基因型者临床症状可能更重.     

脑源性神经营养因子对大鼠惊厥性脑损伤的作用及调控因素

目的观察外源性脑源性神经营养因子（BDNF）、磷酸化cAMP反应元件结合蛋白（pCREB）在活体内对海马BDNF表达的影响及其与神经元凋亡间的关系。方法80只Wistar大鼠,选取40只作为持续惊厥状态（SC）组,制作Wistar鼠SC模型,进一步分为SC-对照亚组（脑室内不注射）、SC-NS亚组（脑室内注射生理盐水）、SC-BDNF亚组（脑室内注射BDNF）和SC-抗pCREB抗体亚组（脑室内注射抗pCREB抗体）,每组各10只大鼠。余下40只大鼠作为对照（NC）组,不制备SC模型,进一步分组和处理方法同SC组。采用ELISA检测海马BDNF含量（pg·μg^-1）,Annexin-V检测海马细胞凋亡。结果①NC-BDNF亚组,注射侧海马BDNF含量为17.24±2.23,明显高于NC-对照亚组5.91±1.63;与NC-对照亚组相比,SC-对照亚组BDNF含量增高,达13.37±5.61。与SC-NS亚组相比,SC-BDNF亚组海马BDNF含量达55.40±4.11,呈显著性增高（P〈0.01）,同时,该侧海马细胞凋亡发生率从（8.36±0.61）%降低至（4.10±1.00）%（P〈0.01）。②NC-抗pCREB抗体亚组注射侧海马BDNF含量为5.94±0.60,与NC-对照亚组差异无统计学意义。与SC-NS亚组（15.77±2.99）相比,SC-抗pCREB抗体亚组注射侧海马BDNF含量急剧下降,为5.53±1.11,并伴有该侧海马细胞凋亡发生率的增加,由（8.36±0.61）%增至（9.37±2.50）%。③脑室内注射将诱导注射侧海马神经细胞凋亡,而对注射对侧海马影响不大。结论①脑室内注射外源性BDNF可影响同侧海马内源性BDNF表达,并对神经元凋亡有一定抑制作用。②选择性阻断CREB的磷酸化,可能通过抑制BDNF的表达,导致神经细胞凋亡。     

白藜芦醇对高脂饮食去卵巢肥胖大鼠海马组织脑源性神经营养因子水平的影响

 目的：探讨去卵巢联合高脂饮食诱导的肥胖大鼠海马组织中脑源性神经营养因子（BDNF）、雌激素受体α (ERα)和雌激素受体β (ERβ) 表达的变化,同时观察白藜芦醇对这些改变的影响。方法：50只3月龄雌性Wistar大鼠随机分为5组：假手术普通饮食对照（C）组、假手术高脂饮食（H）组、单纯去卵巢（O）组、去卵巢高脂饮食（O+H）组和白藜芦醇（40 mg·kg-1·d-1）+去卵巢高脂饮食(O+H+R)组。3月后抽取股动脉血检测血清雌二醇（E2）、总胆固醇（TC）、甘油三酯（TG）、高密度脂蛋白胆固醇（HDL-C）和低密度脂蛋白胆固醇(LDL-C)含量;实时荧光定量PCR法检测海马BDNF、ERα和ERβ mRNA表达,蛋白免疫印迹法及ELISA法分别检测海马BDNF蛋白含量。结果：与C组比较,H组大鼠血清TC和LDL-C含量升高,海马BDNF水平显著降低（P<0.05或P<0.01）,O组大鼠血清E2水平降低,TC含量升高,海马BDNF 水平及ERα、ERβ mRNA表达均明显下降（P<0.05或P<0.01）;O+H组大鼠血清TC含量升高,HDL-C水平降低,海马BDNF 水平降低,与C组、H组和O组比较均有显著差异（P<0.05或P<0.01）,海马ERα和ERβ mRNA表达下降,与C组和H组比较差异显著（P<0.05或P<0.01）;O+H+R组大鼠血清E2水平升高,TC含量降低,海马ERα和ERβ mRNA表达水平及BDNF含量均明显增加,与O+H组比较有显著差异（P<0.05或P<0.01）。结论：去卵巢联合高脂饮食显著降低大鼠海马ERα和ERβ mRNA表达及BDNF水平,而白藜芦醇能够明显改善绝经后肥胖大鼠的血脂水平,上调海马ERα和ERβ mRNA表达,增加海马BDNF水平。