BDNF对急性高眼压后大鼠视网膜三种钙结合蛋白表达的影响

目的：检测外源性BDNF对急性高眼压后大鼠视网膜Parvalbumin（PV），calbindin D-28k（CB）和calretinin（CR）表达的影响。方法：72只SD大鼠随机分成高眼压组、溶媒预处理高眼压组和BDNF预处理高眼压组，每组动物左眼制作急性高眼压模型，右眼为正常对照，动物分别存活1、3、7或14d。用免疫组化方法检测视网膜PV、CB和CR的表达变化。结果：溶媒预处理高眼压组中PV、CB和CR的表达与高眼压组相似。高眼压组中，随着再灌时间延长，内层视网膜中PV和CB标记的神经元数先下调再逐渐恢复，而CR标记的神经元数逐渐减少；再灌1d时PV和CR具有从内核层到内网层的重新分布。在BDNF预处理高眼压组，PV、CB和CR标记的神经元数在再灌1d、7d和14d时与高眼压组比较无明显差异，但在再灌3d时，明显高于后者（P〈0．05）。结论：BDNF预处理对急性高眼压后视网膜的保护作用可能与其再灌早期上调钙结合蛋白的表达有关。     

Developmental changes in concentrations and distributions of neurotrophins in the monkey cerebellar cortex

Neurotrophins are involved in the survival, differentiation, migration and neurite outgrowth of various neuronal populations. Neurotrophins and their receptors are widely expressed in the developing cerebellum of various experimental animals. To gain some insight into the possible roles played by these molecules in monkey cerebellum, we examined the protein levels of BDNF, NT-4/5 and NT-3 and distributions of those neurotrophins and TrkC, a high affinity receptor for NT-3, in the cerebellum of developing macaque monkeys using ELISAs and immunohistochemical methods. We found that the level of BDNF increased during development, while the level of NT-3 was higher during embryonic stages and decreased toward adulthood. The level of NT-4/5 increased from embryonic stages to infant stages and gradually declined with age. Among the three neurotrophins, BDNF immunoreactivity was found in all kinds of cerebellar neurons, including all inhibitory interneurons, throughout the postnatal periods examined, indicating that BDNF may be an essential factor for the maintenance of cerebellar neural functions. The Bergmann glial fibers and the internal part of the external granule cell layer were strongly NT-3 immunopositive at the early postnatal stages, and more weakly immunoreactive toward adulthood. In addition, we found that the premigratory precursors of the granule cells were TrkC immunopositive at early postnatal stages. These findings suggest that NT-3 in Bergmann glial fibers may be involved in the migration of the premigratory granule cells.     

BDNF对体外培养的大鼠脊髓前角神经元内突触素Ⅰ与突触囊泡素表达的影响

探讨BDNF对体外培养的大鼠脊髓前角神经元内突触素I与突触囊泡素(SYN)表达的影响。取孕14d大鼠子宫内胎鼠的脊髓腹侧部分神经元,体外有血清培养。在培养7d后,随机分成对照组、BDNF组和抗BDNF组。BDNF组培养液中加入BDNF(20ng/ml),抗BDNF组培养液中加入BDNF抗体(20μg/ml),对照组加入等量Hanks液。3d后在倒置显微镜下计数三组神经元存活数,并用NF200、MAP2、NSE的免疫组化反应对神经细胞进行鉴定。行突触素I与SYN免疫组化反应,对部分细胞行突触素ImRNA原位杂交反应,运用图像分析系统对突触素I与SYN免疫组织反应阳性产物以及突触素I原位杂交反应阳性产物作光密度分析。结果发现有血清培养时各组脊髓前角神经元的存活数无显著差异(P>0.05);BDNF组突触素I与SYN免疫反应阳性产物的平均光密度值高于其它两组,抗BDNF组最低(P<0.01)。BDNF组突触素ImRNA阳性产物的平均光密度值明显高于其它两组,抗BDNF组突触素ImRNA阳性产物的平均光密度值最低(P<0.01)。本研究结果提示BDNF对有血清培养时脊髓前角神经元的存活没有明显影响,但BDNF可明显上调培养的脊髓前角神经元内突触素I与SYN的表达。     

骨髓间质干细胞和脑源性神经营养因子联合应用促进兔脊髓外伤性截瘫的修复

目的:观察骨髓间质干细胞(bone m arrow strom a cells,BM SCs)和脑源性神经营养因子(brain derived neurotrophic factor,BD N F)联合应用对兔脊髓外伤性截瘫结构和功能修复的影响,以寻求建立一种更有效的治疗脊髓外伤性截瘫的疗法。方法:采用改良A llen打击法建立兔脊髓外伤性截瘫的模型,模型建立成功后观察3d再分别行注射生理盐水(对照组)、BM SCs、BD N F和BM SCs BD N F干预。脊髓损伤移植后1、3、5周进行改良Tarlov评分及CSEP评测,5周观察脊髓结构的变化。结果:与BM SCs组、BD N F组相比,移植后第5周,BM SCs BD N F联合移植组脊髓损伤处结构恢复较好,第3周、5周后,BM SCs BD N F组的CSEP和改良Tarlov评分亦明显好于BM SCs组和BD N F组(P<0.01)。结论:BM SCs和BD N F联合移植对急性脊髓外伤性截瘫的结构和功能有更好的修复作用。     

Induction of tyrosine kinase receptor b by retinoic acid allows brain-derived neurotrophic factor-induced amyloid precursor protein gene expression in human SH-SY5Y neuroblastoma cells

Retinoic acid (RA) is a potent regulator of morphogenesis, growth and cell differentiation. Incubation with RA causes arrest of proliferation and neurite extension in SH-SY5Y cells, a neuroblastoma cell line of human origin. In these cells, RA regulates the expression of the β-amyloid precursor protein. The retinoid increases the levels of intracellular and secreted forms of APP (amyloid precursor protein), APP–mRNA levels and the activity of the APP promoter in transient transfection studies. These responses require long periods of exposition to the ligand, thus suggesting a nondirect effect of the RA receptors on the APP gene. Also in these cells, RA induces the expression of TrkB, the tyrosine kinase receptor for brain-derived neurotrophic factor (BDNF), and 4 days of pretreatment with retinoic acid confers BDNF responsiveness to the APP promoter.     

基于BDNF/TrkB/p-CREB信号通路探讨血府逐瘀胶囊促进神经再生防治卒中后抑郁的作用及机制

目的 探讨血府逐瘀胶囊对卒中后抑郁（post-stroke depression,PSD）大鼠抑郁症状的改善作用,并基于神经再生关键通路脑源性神经营养因子（brain derived neurotrophic factor,BDNF）/酪氨酸激酶受体B(tyrosine kinase receptor,TrkB)/磷酸化环腺苷酸应答元件结合蛋白（phosphorylated cAMP response element-binding protein,p-CREB）探讨其机制。方法 采用短暂大脑中动脉梗塞（transient middle cerebral artery occlusion,tMCAO）复合慢性不可预知应激（chronic unpredictable mild stimulation,CUMS）方法复制PSD大鼠模型。大鼠随机分为假手术组、模型组及血府逐瘀低、高剂量（0.43、0.86 g/kg）组和氟西汀（1.8 mg/kg）组,每组18只。连续给予药物干预28 d,利用神经功能评分、糖水偏好实验、旷场实验、强迫游泳实验考察血府逐瘀胶囊对PSD大鼠神经功能损伤以及抑郁症...     

Effect of high-BDNF microenvironment stem cells therapy on neurogenic bladder model in rats

BackgroundThe purpose of this study is to explore the effects of high-BDNF microenvironment produced by engineered immortalized mesenchymal stem cells (imMSCs) on the neurogenic bladder (NB) and investigate underlying mechanism.MethodsMale Sprague-Dawley rat (12-week-old, weighing about 370–400 g) were purchased from a Korean company (Orient Bio Co. Seongnam, Korea) and divided into the following groups (n=32): sham control group (n=8), NB group (n=8), NB + ImMSCs group (n=8), NB + ImMSCs (BDNF) group (n=8). The major pelvic ganglion (MPG) was observed under anesthesia. Three NB groups of rats were then subjected to bilateral MPG injury. The sham control group of rats was treated with sham surgery. Cystometry were performed before the rats were sacrificed, and then MPG and bladder were collected for histochemical and Western blot analysis.ResultsMSCs treatment improves lower urinary tract function, and the NB + ImMSCs (BDNF) group is better than the NB + ImMSCs group (P<0.01). MSCs treatment accelerates recovery of injured nerve tissue, and the NB + ImMSCs (BDNF) group is better than the NB + ImMSCs group (P<0.01). In high BDNF environment, apoptosis was reduced more significantly and muscle tissue recovered more rapidly (P<0.01). High-BDNF microenvironment activates more BDNF/TrkB/CREB signaling pathways (P<0.01).ConclusionsIn a rat NB model caused by nerve injury, imMSCs have certain effects on nerve tissue repair. At the same time, it was proved that increasing the expression of BDNF which had specific effect on nerve injury repair could more effectively repair injured MPG in local microenvironment. The mechanism may be related to the activation of the BDNF/TrkB/CREB signaling pathway and the reduction of apoptosis by highly expressed BDNF.     

The neurostructural and neurocognitive effects of physical activity: A potential benefit to promote eating disorder recovery

Accumulating evidence suggests that supervised and adapted physical activity provides cognitive benefits for individuals with eating disorders (EDs). The mechanisms underlying the benefits of physical activity are poorly understood. Addressing this knowledge gap may inform the appropriate integration of structured physical activity into eating disorders treatment and recovery. We draw attention to recent findings in the study of the impact of physical activity on the brain, and we describe the neurostructural and neurocognitive changes associated with physical activity observed in various clinical and nonclinical populations. Considering the identified impairment in brain volume- and/or neurocognitive function in various EDs, we propose that positive effects of physical activity may play a meaningful role in successful ED treatment. Accordingly, we outline research steps for closing the knowledge gap on how physical activity may aid in ED recovery, and emphasize the need to combine measures of cognitive and behavioral responses to physical activity, with technology capable of measuring changes in brain structure and/or function.     

Mild experimental brain injury differentially alters the expression of neurotrophin and neurotrophin receptor mRNAs in the hippocampus

The molecular events responsible for impairments in cognition following mild traumatic brain injury are poorly understood. Neurotrophins, such as brain-derived neurotrophic factor (BDNF), have been identified as having a role in learning and memory. We have previously demonstrated that following experimental brain trauma of moderate severity (2.0-2.1 atm), mRNA levels of BDNF and its high-affinity receptor, trkB, are increased bilaterally in the hippocampus for several hours, whereas NT-3 mRNA expression is decreased. In the present study, we used in situ hybridization to compare BDNF, trkB, NT-3, and trkC mRNA expression in rat hippocampus at 3 or 6 h after a lateral fluid percussion brain injury (FPI) of mild severity (1.0 atm) to sham-injured controls at equivalent time points. Mild FPI induced significant increases in hybridization levels for BDNF and trkB mRNAs, and a decrease in NT-3 mRNA in the hippocampus. However, in contrast to the bilateral effects of moderate experimental brain injury, the present changes with mild injury were restricted to the injured side. These findings demonstrate that even a mild traumatic brain injury differentially alters neurotrophin and neurotrophin receptor levels in the hippocampus. Such alterations may have important implications for neural plasticity and recovery of function in people who sustain a mild head injury.     

Chronic supranigral infusion of BDNF in normal and MPTP-treated common marmosets

Summary. BDNF or vehicle were administered by unilateral supranigral infusion in normal and chronically lesioned MPTP-treated common marmosets (Callithrix jacchus) for four weeks and locomotor activity, disability and response to apomorphine were assessed with nigral TH, GFAP and GAD immunoreactivity and striatal [³H]mazindol autoradiography. Selective contraversive orientation and ipsilateral neglect evolved in MPTP-treated marmosets receiving BDNF with no significant difference in disability or locomotor activity when compared to the vehicle-infused group. Apomor-phine produced an ipsiversive rotational bias in BDNF-treated animals. In normal animals infused with BDNF contralateral neglect, ipsiversive turning, postural instability and ataxia rapidly evolved. In MPTP-treated marmosets BDNF caused increased ipsilateral striatal [³H]mazindol binding with increased somatic size and staining intensity in GAD-immunoreactive cells and a 10–20% loss of nigral TH-immunoreactive cells with increased GFAP staining. In normal common marmosets, both vehicle and BDNF infusion decreased nigral TH-immunoreactivity. Chronic supranigral infusion of BDNF alters motor behaviour and spatial attention in MPTP-treated marmosets which may reflect altered function in residual nigral dopaminergic neurons and brainstem GABAergic neurons and in normal animals produces behavioural and histological signs of nigrostriatal hypofunction. Received September 1, 1998; accepted December 17, 1998