Protective effect of chronic caffeine intake on gene expression of brain derived neurotrophic factor signaling and the immunoreactivity of glial fibrillary acidic protein and Ki-67 in Alzheimer’s disease

Alzheimer’s disease (AD) is a neurodegenerative disorder with progressive degeneration of the hippocampal and cortical neurons. This study was designed to demonstrate the protective effect of caffeine on gene expression of brain derived neurotrophic factor (BDNF) and its receptor neural receptor protein-tyrosine kinase-β (TrkB) as well as glial fibrillary acidic protein (GFAP) and Ki-67 immunoreactivity in Aluminum chloride (AlCl₃) induced animal model of AD. Fifty adult rats included in this study were classified into 5 group (10 rats each); negative and positive control groups (I&II), AD model group (III), group treated with caffeine from the start of AD induction (IV) and group treated with caffeine two weeks before AD induction (V). Hippocampal tissue BDNF and its receptor (TrkB) gene expression by real time RT-PCR in addition to immunohistochemical study of GFAP and Ki67 immunoreactivity were performed for all rats in the study. The results of this study revealed that caffeine has protective effect through improving the histological and immunohistochemical findings induced by AlCl₃ as well as BDNF and its receptor gene expression. It could be concluded from the current study, that chronic caffeine consumption in a dose of 1.5 mg/kg body weight daily has a potentially good protective effect against AD.     

右美托咪定在体外对原代海马神经元氧化应激损伤的影响

目的 探讨右美托咪定在体外减弱原代海马神经元的氧化应激损伤的机制.方法 将培养的原代海马神经元分为5组:空白对照组(C组)、损伤对照组(S组)、右美托咪定组(D组),D1,D2,D3组加入不同剂量的右美托咪定(0.001μmol/L、0.1μmol/L、10μmol/L).利用1 mmol/L的过氧化氢(H2O2)处理原代海马神经元1 h,制作神经元氧化应激损伤模型.按照以上分组情况加入右美托咪定,37℃、5％二氧化碳孵箱孵育6 h.通过测定细胞存活率和上清液中乳酸脱氢酶(LDH)的活性确定减轻海马神经元损伤的右美托咪定的适宜浓度.并检测细胞内丙二醛(MDA)含量、超氧化物歧化酶(SOD)活性的变化.应用逆转录聚合酶链反应(RT-PCR)方法测量各组细胞外信号调节激酶(ERK)1/2和脑源性神经营养因子(BNDF)mRNA表达量.结果 右美托咪定组(0.001μmol/L、0.1μmol/L、10μmol/L)细胞存活率分别为(72.13±2.45)％、(89.34±2.56)％、(78.40±2.60)％,均高于损伤组的(51.04±2.12)％,差异有统计学意义(P<0.05);LDH活性显著低于损伤对照组;0.1μmol/L右美托咪定组对海马神经细胞氧化应激损伤的保护作用最好.0.1μmol/L右美托咪定组海马神经细胞培养上清液中MDA含量及细胞凋亡率显著低于损伤对照组,SOD活性显著高于损伤对照组.RT-PCR法检测结果提示0.1μmol/L右美托咪定组ERK1/2和BNDF mRNA表达量显著高于损伤对照组.结论 适宜剂量的右美托咪定对氧化应激损伤的海马神经元有一定的保护作用,其作用机制可能与其能够提升海马神经细胞的抗氧化能力,从而抑制海马神经元的凋亡有关,这种功能可能与ERK1/2和BNDF信号通路有关.     

Mitochondrial dysfunctions,endothelial progenitor cells and diabetic retinopathy

Aim

Diabetic retinopathy (DR) is the leading cause of vision loss in the working age population. Endothelial progenitor cells (EPC) play a vital role in vascular damage repair. This article will review recent progress regarding mitochondrial and EPC dysfunction associated with DR.

Promoting neuroregeneration by applying dynamic magnetic fields to a novel nanomedicine: Superparamagnetic iron oxide (SPIO)-gold nanoparticles bounded with nerve growth factor (NGF)

Neuroregeneration imposes a significant challenge in neuroscience for treating neurodegenerative diseases. The objective of this study is to evaluate the hypothesis that the nerve growth factor (NGF) functionalized superparamagnetic iron oxide (SPIO)-gold (Au) nanomedicine can stimulate the neuron growth and differentiation under external magnetic fields (MFs), and dynamic MFs outperform their static counterparts. The SPIO-Au core-shell nanoparticles (NPs) (Diameter: 20.8 nm) possessed advantages such as uniform quasi-spherical shapes, narrow size distribution, excellent stabilities, and low toxicity (viability >96% for 5 days). NGF functionalization has enhanced the cellular uptake. The promotion of neuronal growth and orientation using NGF functionalized SPIO-Au NPs, driven by both the static and dynamic MFs, was revealed experimentally on PC-12 cells and theoretically on a cytoskeletal force model. More importantly, dynamic MFs via rotation performed better than the static ones, i.e., the cellular differentiation ratio increased 58%; the neurite length elongation increased 63%.     

Differential Regulation of Nerve Growth Factor (NGF) Synthesis in Neurons and Astrocytes by Glucocorticoid Hormones

Glucocorticoid hormones are important regulators of brain development and ageing. Here we show that dexamethasone, a synthetic glucocorticoid, differentially affects the expression of nerve growth factor (NGF) in cultured neurons and astrocytes. Dexamethasone increased the levels of NGF mRNA in cultured hippocampal neurons in a time- and concentration-dependent manner, whereas it down-regulated the NGF mRNA levels in astrocytes. However, dexamethasone had no effect on the mRNA levels of brain-derived neurotrophic factor in the hippocampal neurons. Aldosterone, a mineralocorticoid, in higher concentrations also up-regulated NGF mRNA levels in the hippocampal neurons. Dexamethasone increased the levels of NGF mRNA in the rat hippocampus in vivo , but not to the same extent as observed with kainic acid, a glutamate receptor agonist. There is no apparent diurnal rhythm in the hippocampal NGF protein levels corresponding to circadian variations in the levels of glucocorticoid hormones in serum. The increase in NGF mRNA in the hippocampus in vivo following dexamethasone treatments may reflect the physiological response of hippocampal neurons to high glucocorticoid levels reached under conditions of stress.     

银杏叶抗抑郁作用

通过查阅近10年来关于银杏叶制剂的药理研究、动物实验和临床试验,将银杏叶的抗抑郁作用机制总结为4个方面,分别是对神经递质类的调节,包括对5-羟色胺、去甲肾上腺素的调节;抗自由基作用保护神经元;类脑源性神经营养因子(BNDF)作用;抗血小板活化因子(PAF)作用增加脑血流量保护神经元,并分析了银杏叶制剂在临床分别于中、西药联用的疗效特点、起效时间和用药周期的特点,总结提出临床抑郁症应早期联合使用银杏叶,发挥其显效快速的特点,并应当推广配合使用,起到预防和治疗老年抑郁症的作用。     

Protective effects of curcumin on acrolein-induced neurotoxicity in HT22 mouse hippocampal cells

Background

Aging is one of the most important inevitable risk factors of Alzheimer disease (AD). Oxidative stress plays a critical role in the process of aging. Curcumin has been proposed to improve neural damage, especially neurodegenerative injury, through its antioxidant and anti-inflammatory properties. Therefore, we investigated the effects of curcumin on acrolein-induced AD-like pathologies in HT22 cells.

中医内服外治综合疗法对糖尿病周围神经病变气虚血瘀证患者疗效的影响及作用机制

目的观察中医内服外治综合疗法治疗糖尿病周围神经病变气虚血瘀证患者的临床疗效及对血清胰岛素样生长因子(IGF-1)和脑源性神经营养因子(BNDF)的影响,探讨其可能的作用机制。方法将72例糖尿病周围神经病变气虚血瘀证患者随机分为治疗组和对照组各36例。在西医基础治疗的同时,治疗组采用中药内服联合中药熏蒸、针灸疗法,对照组仅采用中药内服,疗程均为3个月,观察2组患者临床总有效率,以及治疗前后中医证候积分、Toronto临床评分、神经传导速度及血清IGF-1和BNDF的变化。结果治疗组临床总有效率为91.1%,对照组为82.8%,治疗组的疗效优于对照组(P<0.05)。治疗后,治疗组患者正中神经、腓肠神经、胫神经神经传导速度改善均优于对照组(P<0.05);治疗组患者血清IGF-1和BNDF表达优于对照组(P<0.05)。治疗过程中无明显不良反应,无肝肾功能损害。结论中医内服外治综合疗法可明显改善糖尿病周围神经病变患者的临床症状、神经病变积分及神经传导速度,其作用机制可能与提高血清IGF-1和BNDF表达有关。     

氟西汀对缺血性脑卒中患者脑源性神经营养因子的影响

目的观察氟西汀对缺血性脑卒中患者血清脑源性神经营养因子(brain-derived neurotrophic factor,BDNF)的影响。方法将60例缺血性脑卒中的患者随机分为氟西汀组和安慰剂组,两组患者均同时接受物理治疗。采用酶联免疫吸附法(ELISA)测定两组缺血性脑卒中患者治疗前后BDNF的变化,并与正常对照组比较;用改良Barthel指数(modified Barthel index,MBI)和简化Fugl-Meyer运动功能量表(Fugl-Meyer assessment,FMA)评定两组患者的日常生活活动能力(activties of daily living,ADL)和运动功能。结果治疗3m后,氟西汀组BDNF浓度显著高于治疗前及安慰剂组、对照组(P<0.05);治疗后两组MBI及FMA两项评分均有改善(P<0.05),且氟西汀治疗组疗效优于对照组(P<0.05)。结论缺血性脑卒中患者早期给氟西汀和物理治疗后可促进其运动功能的恢复,提高日常生活活动能力,这种效应可能是通过提高BDNF的浓度,促进神经元再生和对抗神经元损伤后凋亡而发挥作用。