抑郁症患者应用无抽搐电休克治疗对患者血清脑源性神经营养因子的影响

目的分析抑郁症患者应用无抽搐电休克治疗对患者血清脑源性神经营养因子的影响。方法将160例抑郁症患者按照入院先后顺序依次编号,采用数字随机表法分组,单号为研究组,双号为对照组。对照组采用艾司西酞普兰治疗;研究组采用艾司西酞普兰联合无抽搐电休克治疗。结果治疗前,2组患者BDNF水平比较无显著差异(P0.05);治疗后,2组患者均出现明显升高,与治疗前比较差异有统计学意义(P0.05);但研究组优于对照组(P0.05)。研究组治疗有效率为92.50%(74/80)与对照组82.50%(66/80)比较差异有统计学意义(P0.05)。同时2组患者治疗前后HAMD、HAMA及CGI、认知功能均得到明显改善(P0.05)。此外,2组患者均未发生性功能障碍等不良反应。结论采用无抽搐电休克治疗抑郁症,有效改善患者抑郁、焦虑及认知功能,提高患者BDNF水平,对患者性功能无影响,是一种安全有效的治疗方式,值得推广应用。     

精神分裂症患者改良电休克治疗前后血清胶质源性神经营养因子水平的变化

目的:探讨改良电休克治疗(MECT)对精神分裂症(SZ)患者血清胶质源性神经营养因子(GDNF)水平的影响。方法:采用酶联免疫吸附法,对48名正常人(对照组)和70例SZ患者(患者组)在MECT前后进行血清GDNF水平检测。结果:MECT前,患者组血清GDNF水平[(34.98±20.36)ng/ml]显著低于对照组[(78.23±40.57)ng/ml](t=6.821,P0.001)。MECT后,患者组血清GDNF水平[(79.88±36.10)ng/ml]显著升高,与MECT前比较有显著差异(t=-10.64,P0.01),与对照组差异无统计学意义(t=-0.232,P0.05)。结论:SZ患者可能存在血清GDNF水平低下,MECT可能通过提高GDNF水平起作用。     

抑郁症血清胶质源性神经营养因子与生活事件

目的:研究抑郁症患者血清胶质源性神经营养因子(GDNF)水平变化及其与生活事件之间的关系. 方法:76例未经药物治疗的抑郁症患者(患者组),采用生活事件量表(LES)和汉密尔顿抑郁量表(HAMD)进行评定.用酶联吸附反应方法对患者进行血清GDNF检测,并与50名正常人(对照组)进行对照比较. 结果:患者组血清GDNF水平平均为(343.3±201.3)pg/ml,显著低于对照组的GDNF水平平均(749.9±300.4)pg/ml(t=8.41,P<0.001).以LES评分200分为界,将抑郁症患者分为高应激状态(n=23例)和低应激状态(n=53例),高应激状态患者的血清GDNF水平平均为(244.3±144.1)pg/ml,显著低于低应激状态患者的平均(386.2±208.5)pg/ml(t=2.97,P<0.001).LES总分和血清GDNF水平之间呈显著负相关(r=-0.291,P<0.05). 结论:抑郁症患者可能存在GDNF水平下降,应激对血清GDNF水平可能有调节作用.     

无抽搐电休克治疗难治性抑郁症的对照研究

目的探讨无抽搐电休克治疗难治性抑郁症的疗效及安全性。方法将52例难治性抑郁症患者随机分为研究组25例（在原抗抑郁治疗方案基础上联合无抽搐电休克）和对照组27例（继续原抗抑郁治疗方案）,共观察4周,在治疗前及治疗第1,2,4周末采用汉密尔顿抑郁量表（HAMD）、治疗副反应量表（TESS）评定疗效及不良反应。结果研究组显效率为65．0％,明显高于对照组的18．5％（P〈0．01）。结论无抽搐电休克治疗是治疗难治性抑郁症安全有效的方法。     

胶质源性神经营养因子和精神分裂症相关性的研究进展

目前神经发育异常假说认为精神分裂症是脑组织发育异常的结果。胶质细胞源性神经营养因子(GDNF)对神经细胞的生长、分化、存活、可塑性及损伤后修复有重要作用。GDNF基因敲除小鼠表现出异常的海马突触传递,GDNF及其受体在海马、前额皮质均有高表达,而这些脑区与精神分裂症的发生与治疗有关。故本文对GDNF和精神分裂症的关系作一综述。     

胶质细胞源性神经营养因子研究进展

神经营养因子(neurotrophines, NTs)是一组多肽因子,可特异性地作用于某一种神经元或广谱地作用于多种神经元,促进神经元的存活和诱导突起生长.神经营养因子为一个大家族,参与神经系统的生长发育,功能维持和损伤修复.     

无抽搐电休克治疗——无抽搐电休克对难治性精神分裂症的增效作用

目的：探讨无抽搐电休克治疗（MECT）对难治性精神分裂症的疗效和安全性。方法：76例难治性精神分裂症患者随机分为合用组（药物联合MECT）和单用组（单用药物治疗），每组各38例。合用组自药物治疗3周起增加MECT，疗程12周。采用阳性与阴性症状量表（PANSS）和治疗中出现的症状量表（TESS）评定疗效和不良反应;韦氏记忆量表（WMS）评定MECT对记忆力的影响。结果：合用组总有效率84.2%和显效率55.3%显著高于单用组的60.5%和31.6%（χ^2=4.34，5.33;P均〈0.05）;两组PANSS总分及各因子分均较治疗前有显著下降（P均〈0.01），以合用组显著低于单用组（P〈0.01或P〈0.05）;WMS评分与治疗前比较差异无显著性（P〉0.05）。两组不良反应发生率和TESS评分差异无显著性（P〉0.05）。结论：MECT对难治性精神分裂症有较好的增效作用，不良反应少。     

胶质细胞源性神经营养因子与脑缺血

胶质细胞源性神经营养因子 (GDNF)是转化生长因子(TGF- β)超家族成员 ,最近已被纯化并克隆 ,是一个最有效的营养因子。对 GDNF的研究始于十年前 ,Schubert等为了研究神经系统中不同细胞系蛋白的表达 ,用两种不同规格的凝胶进行电泳检测 ,比较不同克隆的神经元和胶质细胞系蛋白表达情况 ,结果发现电泳带是完全不同的。当时由于缺乏对较低含量蛋白的分离和鉴别技术而未能进一步研究 [1 ] 。后来发现胶质细胞系 B49、R33和 JSC1具有分泌促进多巴胺脑神经元存活的蛋白质 [2 ] 。 1993年 L in等从 B49神经胶质瘤细胞的条件培养液中纯化…     

难治性抑郁症应用无抽搐电休克疗法效果分析

目的观察无抽搐电休克疗法治疗难治性抑郁症(TRD)的效果。方法回顾分析2009-02—2012-12在我院住院治疗的难治性抑郁患者80例的临床资料,随机将80例患者分成2组,对照组40例口服帕罗西汀治疗,观察组40例采用无抽搐电休克疗法治疗,记录2组治疗前与治疗后1周、2周、4周、8周的HAMD、HAMA评分变化,并记录治疗8周期间的不良反应情况。结果治疗前2组HAMD、HAMA评分比较无明显差异(P>0.05),治疗后观察组HAMD、HAMA改善程度明显优于对照组,并随着治疗时间的加长,改善程度更显著(P<0.05)。2组治疗期间的不良反应发生率比较无明显差异(χ2=3.16,P=0.075>0.05)。结论应用无抽搐电休克疗法治疗难治性抑郁症(TRD)效果满意,能显著改善患者的临床症状,安全性强。     

改良电抽搐与抗抑郁药对抑郁症患者血清脑源性神经营养因子影响的对照研究

目的 探讨改良电抽搐治疗(MECT)与抗抑郁药对抑郁症患者血清脑源性神经营养因子(BDNF)的影响.方法 根据性别和年龄相配伍,收集只接受抗抑郁药物治疗(非MECT组)和联合接受MECT治疗的抑郁症患者(MECT组)各24例,检测患者治疗前后和80名正常对照的血清BDNF浓度并作组间比较.结果 治疗前两组抑郁症患者血清BDNF浓度均低于正常对照组(P<0.01);治疗后两组血清BDNF浓度均显著高于治疗前(P<0.01或P＜0.05),MECT组升高幅度明显高于非MECT组(治疗前后均致差分别为20.75和10.10),而两组与正常对照组的差异无统计学意义(F=1.88,P=0.16).两组治疗有效者血清BDNF浓度显著高于治疗前(P<0.01或JP<0.05),治疗无效者治疗前后血清BDNF浓度差异均无统计学意义(P>0.05).结论 MECT和抗抑郁药物治疗均可能通过提高BDNF水平而起到抗抑郁作用.     

Motoneurons crave glial cell line-derived neurotrophic factor

This is a commentary on the developmental and therapeutic relevance of recent studies in the glial fibrillary acid protein (GFAP)-glial cell line-derived neurotrophic factor (GDNF) transgenic mouse reported by Zhao et al. (2004). This interesting study demonstrated that increased expression of GDNF in astrocytes increases the number of neighboring motoneurons of certain motoneuron subpopulations by diminishing programmed cell death during development. In addition, astrocyte-derived GDNF was shown to protect facial motoneurons from injury-induced cell death. Since this is the first direct demonstration that secretion of GDNF from astrocytes in the CNS can affect motoneuron development in utero and motoneuron survival after axotomy, novel approaches for motor neuron disease are suggested. The known target neurons that respond to GDNF are reviewed, as are studies using GDNF gene delivery in animal models of amyotrophic lateral sclerosis (ALS). It is postulated that GDNF is a factor to which many motoneurons respond along their whole extent from soma to axon to terminal.     

Effect of treatment on serum glial cell line-derived neurotrophic factor in depressed patients

Post-mortem studies have demonstrated a decreased number of glia, reduced glial density, and a decreased glia/neuron ratio in different brain areas of patients diagnosed with a major depressive disorder (MDD). Researchers have therefore suggested that neurotrophic growth factor systems might be involved in the aetiology of MDD. This study aimed to test whether glial cell line-derived neurotrophic factor (GDNF), a member of the transforming growth factor beta family, in serum was associated with MDD. Serum concentrations were measured in MDD patients before treatment (n=76), after 8 weeks of antidepressant treatment (n=39), and in control subjects (n=50) using a sandwich ELISA method. Serum GDNF was significantly lower in MDD patients before treatment than in control subjects (P<0.001). From baseline to remission after 8 weeks of treatment, the increase in serum GDNF was statistically significant (P<0.001). The present study suggests that lower serum GDNF might be involved in the pathophysiology of MDD and antidepressant treatment increases the GDNF in MDD.     

Astrocyte delivery of glial cell line-derived neurotrophic factor in a mouse model of Parkinson's disease

Primary astrocytes were genetically modified ex vivo to express recombinant glial cell line-derived neurotrophic factor (GDNF) and subsequently were tested for their ability to provide neuroprotection to dopaminergic neurons in a 6-hydroxydopamine (6-OHDA) mouse model of Parkinson's disease. A replication-defective retrovirus was constructed, which contained the rat GDNF sequence and a sequence encoding a beta-galactosidase (beta-gal)/neomycin phosphotransferase fusion protein, linked via an internal ribosomal entry site. Murine astrocytes transduced with this vector secreted GDNF into the culture media at the rate of 115 +/- 34 pg/24 h/10(5) cells and expressed cytoplasmic beta-gal, whereas control nontransduced astrocytes were negative for GDNF production and cytoplasmic beta-gal expression. Mice that received implants of GDNF-producing astrocytes into the striatum or nigra displayed elevated levels of GDNF compared to mice that received control nontransduced astrocytes. In addition, tissue content of GDNF was increased bilaterally and in brain regions both proximal and distal to the graft, even though astrocyte migration away from the graft site did not occur. Importantly, GDNF-producing astrocytes provided marked neuroprotection of nigral dopaminergic perikarya, and partial protection of striatal dopaminergic fibers, when implanted into the midbrain 6 days prior to a retrograde 6-OHDA lesion, as assessed by tyrosine hydroxylase immunohistochemistry. Similarly, GDNF-producing astrocytes prevented the acquisition of amphetamine-induced rotational behavior in 6-OHDA-treated mice and completely prevented dopamine depletion within the substantia nigra, as assessed by high-performance liquid chromatography. These results indicate that continuous exposure to low levels of GDNF provided by transgenic astrocytes provides marked neuroprotection of nigral dopaminergic neurons. (c)2002 Elsevier Science (USA).     

氟西汀对大鼠星形胶质细胞分泌的胶质源性神经营养因子的影响

目的 探讨氟西汀对大鼠星形胶质细胞分泌的胶质源性神经营养因子(GDNF)的影响.方法 以氟西汀干预体外培养的大鼠海马星形胶质细胞,通过四甲基偶氮唑盐法(MTT)检测不同浓度氟西汀对细胞活力的影响;采用酶联免疫吸附测定法(ELISA)检测细胞培养液GDNF浓度及Real-time PCR法检测GDNFmRNA的表达.结果 (1)氟西汀浓度超过35 μmol/L浓度时,可降低细胞活性,差异有统计学意义(P<0.01或P<0.05);(2)10 μmol/L氟西汀干预星形胶质细胞不同时间后,48 h组细胞培养液GDNF浓度[(68±13)fg/L]高于0 h组[(32±11)fg/L]、6 h组[(34±12)fg/L]、12 h组[(41±17)fg/L]、24 h组[(45±13)fg/L],差异均有统计学意义(P均<0.01);(3)不同浓度氟西汀作用星形胶质细胞48 h后,10 μmol/L浓度组的细胞培养液GDNF浓度[(64±17)fg/L]高于0 μmol/L[(39±15)fg/L]和1 μmoVL浓度组[(39±18)fg/L],差异均有统计学意义(P均<0.05);(4)氟西汀作用星形胶质细胞48 h后,撤离氟西汀24 h后星形胶质细胞仍明显分泌GDNF,差异有统计学意义(P<0.01或P<0.05);(5)不同浓度氟西汀作用星形胶质细胞24 h后,10 μmol/L和20 μmol/L浓度组细胞GDNFmRNA表达量[分别为(0.008 1±0.001 1)和(0.006 3±0.000 3)]高于0 μmol/L、1 μmol/L及5 μmol/L浓度组[分别为(0.003 1±0.000 7)、(0.003 9±0.000 3)和(0.004 1±0.000 2)],差异均有统计学意义(P均<0.01).结论 氟西汀可能通过促进星形胶质细胞GDNF的分泌来发挥其神经保护作用.     

Dissociation between short-term increased graft survival and long-term functional improvements in Parkinsonian rats overexpressing glial cell line-derived neurotrophic factor

The present study was designed to analyse whether continuous overexpression of glial cell line-derived neurotrophic factor (GDNF) in the striatum by a recombinant lentiviral vector can provide improved cell survival and additional long-term functional benefits after transplantation of fetal ventral mesencephalic cells in Parkinsonian rats. A four-site intrastriatal 6-hydroxydopamine lesion resulted in an 80-90% depletion of nigral dopamine cells and striatal fiber innervation, leading to stable motor impairments. Histological analysis performed at 4 weeks after grafting into the GDNF-overexpressing striatum revealed a twofold increase in the number of surviving tyrosine hydroxylase (TH)-positive cells, as compared with grafts placed in control (green fluorescent protein-overexpressing) animals. However, in animals that were allowed to survive for 6 months, the numbers of surviving TH-positive cells in the grafts were equal in both groups, suggesting that the cells initially protected at 4 weeks failed to survive despite the continued presence of GDNF. Although cell survival was similar in both grafted groups, the TH-positive fiber innervation density was lower in the GDNF-treated grafted animals (30% of normal) compared with animals with control grafts (55% of normal). The vesicular monoamine transporter-2-positive fiber density in the striatum, by contrast, was equal in both groups, suggesting that long-term GDNF overexpression induced a selective down-regulation of TH in the grafted dopamine neurons. Behavioral analysis in the long-term grafted animals showed that the control grafted animals improved their performance in spontaneous motor behaviors to approximately 50% of normal, whereas the GDNF treatment did not provide any additional recovery.     

胶质细胞系源性神经营养因子对帕金森病大鼠黑质钙结合蛋白表达的影响

目的研究胶质细胞系源性神经营养因子(GDNF)对帕金森病(PD)大鼠黑质钙结合蛋白(CB)表达的影响,以及神经细胞黏附分子(NCAM)在其中的作用。方法制作PD模型大鼠36只,分为GD-NF组、NCAM阻断组和对照组,每组12只。采用免疫组化染色和免疫印迹法,检测各组大鼠黑质CB阳性细胞数和CB表达量。结果GDNF组黑质处CB阳性神经元数(46.50±6.28)及表达量(33770.60±6929.76)明显高于对照组[(27.00±8.60)、(18281.00±5266.78)](均P<0.05);与NCAM阻断组[(44.00±13.37)、(30857.00±7484.87)]相比差异无统计学意义(均P>0.05)。结论GDNF可上调PD大鼠黑质CB的表达,从而保护受损的多巴胺能神经元,NCAM对这一作用无明显影响。     

多发性硬化、视神经脊髓炎患者血清及脑脊液中脑源性神经营养因子与胶质细胞源性神经营养因子水平

目的 探讨多发性硬化(MS)、视神经脊髓炎(NMO)患者血清及脑脊液中脑源性神经营养因子(BDNF)、胶质细胞源性神经营养因子(GDNF)水平及其神经保护作用.方法 对62例MS、NMO患者及21例对照者进行研究,患者组复发期进行扩展残疾状态量表(EDSS)评分、MRI检查及寡克隆带测定,液相芯片分析技术检测血清及脑脊液BDNF、GDNF浓度.结果 MS、NMO患者复发期血清及脑脊液BDNF(μg/L,MS患者:5.616±0.650、0.186±0.012;NMO患者6.584±0.929、0.176±0.006)、GDNF浓度(μg/L,MS患者:0.039、0.080;NMO患者0.029、0.050)与对照组(μg/L,血清:4.374±0.501、0.040;脑脊液:0.152±0.011、0.065)比较差异无统计学意义;脑脊液BDNF与GDNF浓度水平呈正相关(r=0.756,P=0.000),血清BDNF与GDNF浓度水平呈负相关(r=-0.329,P=0.018).血清及脑脊液BDNF、GDNF浓度与EDSS评分、血脑屏障指数、Delpech指数及Tourtellotte合成率无明显相关性.有或无脑萎缩的MS、NMO患者血清及腩脊液BDNF、GDNF浓度差异无统计学意义.结论 MS、NMO患者体内BDNF与GDNF水平相关,二者可能具有协同的神经保护作用.BDNF及GDNF与NMO、MS患者血脑屏障破坏及中枢神经系统内IgG合成无关,与神经功能残疾及脑萎缩的关系仍需研究.     

Variations in glial cell line-derived neurotrophic factor release from biodegradable nerve conduits modify the rate of functional motor recovery after rat primary nerve repairs

Accelerating axonal regeneration to shorten the delay of reinnervation and improve functional recovery after a peripheral nerve lesion is a clinical demand and an experimental challenge. We developed a resorbable nerve conduit (NC) for controlled release of glial cell line-derived neurotrophic factor (GDNF) with the aim of assessing motor functional recovery according to the release kinetics of this factor in a short gap model. Different types of resorbable NCs were manufactured from a collagen tube and multiple coating layers of poly(lactide-coglycolide), varying in poly(lactide-coglycolide) type and coating thickness to afford three distinct release kinetics of the neurotrophic factor. GDNF release was quantified in vitro. End-to-end suture and GDNF-free NC served as controls. Thirty-five Wistar rats underwent surgery. Motor recovery was followed from 1 to 12 weeks after surgery by video gait analysis. Morphometrical data were obtained at mid-tube level and distal to the NC. NCs were completely resorbed within 3 months with minimal inflammation. GDNF induced a threefold overgrowth of fibers at mid-tube level. However, the number of fibers was similar in the distal segment of all groups. The speed of recovery was inversely proportional to the number of fibers at the NC level but the level of recovery was similar for all groups at 3 months. The resorbable conduits proved their ability to modulate axonal regrowth through controlled release of GDNF. In relation to the dose delivered, GDNF strikingly multiplied the number of myelinated fibers within the NC but this increase was not positively correlated with the return of motor function in this model.     

尼莫地平对大鼠面神经损伤的保护作用及GDNF表达的影响

目的 探讨尼莫地平对大鼠面神经损伤的保护作用及对胶质细胞源性神经生长因子(GDNF)表达的影响.方法 96只大鼠按随机数字表法分为假手术组、单纯损伤组、尼莫地平预处理组、尼莫地平后处理组,后三组建立大鼠面神经电损伤模型.应用HE染色、Western blotting等方法,观察大鼠面神经损伤后不同时期(1、3、6月)GDNF的动态表达变化及尼莫地平不同给药时间对其表达的影响.结果 与单纯损伤组相比,尼莫地平预处理组大鼠面神经损伤程度减轻,GDNF表达升高,持续时间延长;尼莫地平预处理组GDNF表达和尼莫地平后处理组间比较差异有统计学意义(P＜0.05);尼莫地平后处理组GDNF表达在3月、6月时与单纯损伤组比较差异无统计学意义(P＞0.05).结论 预防性应用尼莫地平可以保护面神经,其机制可能是通过调节GDNF的表达而实现的.

Abstract：

Objective To study the protective function of nimodipine on facial nerve injury and its effect on the expression of glial cell line-derived neurotrophic factor (GDNF). Methods Ninety-six SD rats were randomly divided into sham-operated group, facial nerve injury group, nimodipine pretreatment group, and nimodipine post-treatment group. Rat models of facial nerve injury in thc later 3groups were established. The dynamic changes of expression of GDNF were observed by HE staining and Western blotting in different treatment groups and at different time points (1, 3 and 6 months after the injury). Restdts Compared with the facial nerve injury group, the nimodipine pretreatment and post-treatment groups had significantly less severe nerve damage and significantly up-rcgulated expression of GDNF (P＜0.05). The expression of GDNF in the nimodipine pretreatment group was statistically higher than that in the nimodipine post-treatment group (P＜0.05). However, the expression of GDNF in the nimodipine post-treatment group was not statistically different from that in the facial nerve injury group 3 and 6 months after the injury (P＞0.05). Conclusion Nimodipine has significant facial nerve protective effect, and one of the mechanisms of nimodipine to protect the facial nerve is to regulate the GDNF expression.     

Transfection of the glial cell line-derived neurotrophic factor gene promotes neuronal differentiation简

Glial cell line-derived neurotrophic factor recombinant adenovirus vector-transfected bone marrow mesenchymal stem cells were induced to differentiate into neuron-like cells using inductive medium containing retinoic acid and epidermal growth factor. Cell viability, micro- tubule-associated protein 2-positive cell ratio, and the expression levels of glial cell line-derived neurotrophic factor, nerve growth factor and growth-associated protein-43 protein in the su- pernatant were significantly higher in glial cell line-derived neurotrophic factor/bone marrow mesenchymal stem cells compared with empty virus plasmid-transfected bone marrow mes- enchymal stem cells. Furthermore, microtubule-associated protein 2, glial cell line-derived neurotrophic factor, nerve growth factor and growth-associated protein743 mRNA levels in cell pellets were statistically higher in glial cell line-derived neurotrophic factor/bone marrow mesen- chymal stem cells compared with empty virus plasmid-transfected bone marrow mesenchymal stem cells. These results suggest that glial cell line-derived neurotrophic factor/bone marrow mesenchymal stem cells have a higher rate of induction into neuron-like cells, and this enhanced differentiation into neuron-like cells may be associated with up-regulated expression of glial cell line-derived neurotrophic factor, nerve growth factor and growth-associated protein-43.