MPTP-induced changes in hippocampal synaptic plasticity and memory are prevented by memantine through the BDNF-TrkB pathway

Background and Purpose

Mild cognitive deficit in early Parkinson''s disease (PD) has been widely studied. Here we have examined the effects of memantine in preventing memory deficit in experimental PD models and elucidated some of the underlying mechanisms.

Experimental Approaches

I.p. injection of 1-methyl-4- phenyl-1,2,3,6-tetrahydro pyridine (MPTP) in C57BL/6 mice was used to produce models of PD. We used behavioural tasks to test memory. In vitro, we used slices of hippocampus, with electrophysiological, Western blotting, real time PCR, elisa and immunochemical techniques.

Key Results

Following MPTP injection, long-term memory was impaired and these changes were prevented by pre-treatment with memantine. In hippocampal slices from MPTP treated mice, long-term potentiation (LTP) –induced by θ burst stimulation (10 bursts, 4 pulses) was decreased, while long-term depression (LTD) induced by low-frequency stimulation (1 Hz, 900 pulses) was enhanced, compared with control values. A single dose of memantine (i.p., 10 mg·kg⁻¹) reversed the decreased LTP and the increased LTD in this PD model. Activity-dependent changes in tyrosine kinase receptor B (TrkB), ERK and brain-derived neurotrophic factor (BDNF) expression were decreased in slices from mice after MPTP treatment. These effects were reversed by pretreatment with memantine. Incubation of slices in vitro with 1-methyl-4-phenylpyridinium (MPP⁺) decreased depolarization-induced expression of BDNF. This effect was prevented by pretreatment of slices with memantine or with calpain inhibitor III, suggesting the involvement of an overactivated calcium signalling pathway.

Conclusions and Implications

Memantine should be useful in preventing loss of memory and hippocampal synaptic plasticity in PD models.     

中医药戒毒研究的思路与方法

当前,吸毒已成为全世界越来越严重的社会问题,药物依赖这一特殊的疾病已渐渐成为医学界关注的热点。由于本病机制复杂,涉及因素众多,现代医学尚未找到根治之法,目前常用的戒毒药物亦存在一定的副作用或成瘾性。中医药戒毒凭借其理论独到、副作用相对较小、临床疗效明显等特点已日益受到人们的重视,可为戒毒领域的研究提供新的思路。但由于中医戒毒的现代研究起步较晚,目前仍存在一些不足,针对于此,文章较系统地分析了现今中医戒毒工作中存在的问题,并提出了相应的研究思路和方法,以促进其进一步发展,为我国乃至世界戒毒工作做出自己的贡献。     

电针治疗轻度认知功能障碍:多中心随机对照研究

目的:验证“通督调髓”电针法干预轻度认知功能障碍(MCI)患者的临床疗效,拟为针灸临床治疗该病提供循证医学A级证据.方法:采用多中心随机对照试验(RCT)的方法,将192例MCI患者随机分为电针组和尼莫地平组,每组96例.电针组采用电针神庭、百会、四神聪、风池隔日1次;尼莫地平组采用口服尼莫地平每日3次,4周为一疗程,共治疗8周.治疗前、治疗1个疗程和治疗2个疗程后分别进行简易精神状态检查表(minimum mental state examination,MMSE)和图形再认测验,结束治疗后的1个月、3个月和6个月分别采用MMSE量表进行随访评价.结果:电针组的总有效率为50.0％(47/94),优于尼莫地平组的34.4％(32/93,P＜0.05).治疗第1疗程后两组MMSE总评分,认知、记忆和言语维度评分组间比较差异均无统计学意义(均P＞0.05);治疗第2疗程后MMSE量表总评分,认知、记忆和视空间技能维度评分两组均有显著提高(均P＜0.01),且电针组优于尼莫地平组(均P＜0.05),但言语维度评分两组间比较差异无统计学意义(P＞0.05).电针组图形再认得分治疗2个疗程后较治疗前显著改善(P＜0.01),并优于尼莫地平组(P＜0.05).治疗后1个月、3个月和6个月的MMSE量表总评分组间比较差异均有统计学意义(均P＜0.01),电针组远期疗效优于尼莫地平组.结论:“通督调髓”电针法和尼莫地平均能显著改善MCI患者的认知功能,电针较尼莫地平更能显著提高MCI患者的综合认知能力和短时记忆能力,且在改善MCI患者认知、记忆和视空间技能维度方面尤佳;在结束治疗后的半年时间内,电针的远期疗效优于尼莫地平.     

Yishen Huoxue decoction(益肾活血方)attenuates unilateral ureter-ic obstruction-induced renal fibrosis and hypoxia-induced reactive oxygen species generation via adenosine monophosphate-activat-ed protein kinase/peroxisome proliferator-activated receptor co-activator-1α/silent mating-type information regulation 2 homolog 3 pathway

OBJECTIVE:To investigate the effeicacy of Yishen Huoxue decoction (YSHX) on renal fibrosis induced by unilateral ureteric obstruction (UUO),and on re-active oxy...     

HCV基因型在流行病和临床上的意义

近年来丙型肝炎病毒（Hepatitis C Virus,HCV）基因型愈来愈受到大家的关注,Simmonds分型法现在应用最为广泛,其分布不仅具有明显的“三间”流行病学特征,而且研究还发现HCV基因型存在多种生物学活性,与传播途径、临床类型、肝病严重程度、临床多样性、抗病毒疗效和疫苗的研发等密切相关。故本文就从HCV基因分型及在流行病和临床上的意义作一概述。     

一种基于可恢复性水印的医学图像认证方法

本文提出了一种适用于医学图像内容认证和保护的可恢复性水印箅法.选取图像的小波重要系数进行SPIHT编码生成水印:使用Arnold变换确定其嵌入块位置并将其加密嵌入剑图像数据低位;通过链式认证结构实现水印信号的检测和图像篡改数据的定位,由 SPIHT解码完成篡改数据的恢复.实验表明,该算法在保证含水印医学图像具有良好视觉透明性的基础上.还可以定位并恢复被篡改区域内容.     

穴位贴敷联合逍遥散加减治疗经前期综合征的临床研究

目的 探讨穴位贴敷联合逍遥散加减治疗经前期综合征（PMS）的临床效果。方法 选取2019年11月至2021年11月新余市中医院收治的60例肝郁型PMS患者作为研究对象,采用抽签法将其分为单一组与联合组,每组各30例。单一组患者采用逍遥散加减治疗,联合组患者采用逍遥散加减治疗联合穴位贴敷治疗。比较两组患者的中医证候积分、治疗效果、汉密尔顿焦虑量表（HAMA）评分。结果 治疗后,两组患者的中医证候积分均低于治疗前,差异有统计学意义（P<0.05）;治疗后,联合组患者的中医证候积分低于单一组,差异有统计学意义（P<0.05）。联合组患者的总有效率高于单一组,差异有统计学意义（P<0.05）。治疗后,两组患者的HAMA评分均低于治疗前,差异有统计学意义（P<0.05）;治疗后,联合组患者的HAMA评分低于单一组,差异有统计学意义（P<0.05）。结论 穴位贴敷联合逍遥散加减治疗能够明显改善PMS相关症状,改善患者焦虑情绪。     

硫辛酸抗神经细胞老化的蛋白质组学分析

目的研究硫辛酸在神经细胞老化过程中对细胞保护作用的蛋白质分子基础。方法采用无血清培养神经母细胞瘤细胞方法建立实验性神经细胞老化模型。设立硫辛酸（IA）作用组和对照组,运用蛋白质组学技术平台,采用双向电泳结合基质辅助激光电离-飞行时间质谱技术分析,并鉴定表达受到硫辛酸调控的蛋白。结果经蛋白质组学技术分析,发现硫辛酸能阻止19个蛋白在老化过程中表达改变,成功鉴定出其中5个蛋白,其中STMN1、TPM4、SERB和PARK7在老化过程中表达下降,DLDH在老化过程中表达上升。结论硫辛酸抗老化保护神经细胞的作用机制涉及到对STMN1、TPM4、SERB、PARK7和DLDH等蛋白的调控。     

Percutaneous Absorption of Nicardipine and Ketorolac in Rhesus Monkeys

Vehicle effects on the percutaneous absorption of nicardipine base, nicardipine hydrochloride, ketorolac acid, and ketorolac tromethamine were determined using the rhesus monkey as an in vivo model for human skin penetration. Vehicles investigated included blends of propylene glycol, trimethylene glycol, ethanol, Azone, Tween 20, water, and long-chain fatty acids. Formulations were prepared such that the compound dose, application area, and percentage saturation of the compound in the vehicle were held constant. Variations in absorption of the compounds were therefore attributable to vehicle effects. Each formulation was applied to three monkeys for a period of 24 hr using 10 Hill Top Chambers. Plasma samples were taken at appropriate intervals for 36 to 48 hr. The results indicated that trimethylene glycol and Tween 20 did not enhance absorption of the test compounds despite claims by other investigators. Azone and ethanol provided moderate enhancement of both the rate and the extent of absorption, while long-chain fatty acids in combination with propylene glycol significantly enhanced penetration. In general, higher fluxes were observed with the more lipophilic compounds nicardipine base and ketorolac acid as compared to the hydrochloride and tromethamine salts.     

栀子提取物中大孔吸附树脂的苯残留量检查

目的测定栀子提取物中大孔吸附树脂残留的苯是否符合限量要求.方法使用气相色谱仪,采用DB-624毛细管色谱柱,以氮气为载气,FID检测器,测定苯.结果栀子提取物中未检出苯,检出限为0.06mg·L-1.结论该方法简便、准确、重复性好,可用于栀子提取物的质量控制.