绞股蓝正丁醇提取物对快速老化小鼠学习记忆的影响及其机制

目的研究绞股蓝正丁醇部位对阿尔茨海默病(AD)模型小鼠学习记忆的影响。方法采用Morris水迷宫方法对小鼠记忆行为进行检测;采用ELISA法测定SOD、GSH-PX和MDA的含量;采用HE法染色观察对小鼠大脑海马组织的影响。结果绞股蓝正丁醇部位能改善老年痴呆小鼠的学习记忆能力;能促进SOD和GSH-PX生成,抑制MDA的生成。结论绞股蓝正丁醇部位可提高AD小鼠的抗氧化能力,从而起到防治AD的作用。     

七氟醚麻醉对新生鼠学习与记忆的影响

目的 探索用七氟醚麻醉发育期小鼠是否会引起成长过程中学习记忆障碍。 方法 实验包括122只新生鼠(出生后7 d)。其中72只分别经七氟醚1.0或0.5最低肺泡有效浓度(minimum alveolar concentration,MAC)麻醉或吸入40% O₂ 2 h,4周或12周行水迷宫实验,记录训练各天潜伏期和游泳速度,以及探索期平台滞留时间和平台穿越次数。另外50只小鼠用于测定七氟醚麻醉(1.0或0.5 MAC)过程(0、1、2 h)中动脉血血气分析。 结果 新生鼠在整个麻醉过程中,pH值、PaCO₂、PaO₂和SaO₂均保持稳定,P>0.05。麻醉后4周,训练期后3 d,对照组小鼠潜伏期明显低于麻醉组,且后2 d,0.5 MAC组小鼠的潜伏期明显短于1.0 MAC组。探索期,对照组小鼠平台停留时间和平台穿越次数均明显高于2组麻醉组。麻醉后12周,1.0 MAC组小鼠在训练第5天潜伏期仍明显延长。探索期,对照组小鼠平台停留时间和(或)平台穿越次数均明显高于麻醉组。 结论 七氟醚麻醉引起新生鼠成长过程中学习与记忆障碍,其程度与药物浓度有关,且随时间推移减弱。     

Toxicological aspects of trans fat consumption over two sequential generations of rats: Oxidative damage and preference for amphetamine

Chronic consumption of processed food causes structural changes in membrane phospholipids, affecting brain neurotransmission. Here we evaluated noxious influences of dietary fats over two generations of rats on amphetamine (AMPH)-conditioned place preference (CPP). Female rats received soybean oil (SO, rich in n-6 fatty acids (FA)), fish oil (FO, rich in n-3 FA) and hydrogenated vegetable fat (HVF, rich in trans fatty acids (TFA)) for two successive generations. Male pups from the 2nd generation were maintained on the same supplementation until 41 days of age, when they were conditioned with AMPH in CPP. While the FO group showed higher incorporation of n-3 polyunsaturated-FA (PUFA) in cortex/hippocampus, the HVF group showed TFA incorporation in these same brain areas. The SO and HVF groups showed AMPH-preference and anxiety-like symptoms during abstinence. Higher levels of protein carbonyl (PC) and lower levels of non-protein thiols (NPSH) were observed in cortex/hippocampus of the HVF group, indicating antioxidant defense system impairment. In contrast, the FO group showed no drug-preference and lower PC levels in cortex. Cortical PC was positively correlated with n-6/n-3 PUFA ratio, locomotion and anxiety-like behavior, and hippocampal PC was positively correlated with AMPH-preference, reinforcing connections between oxidative damage and AMPH-induced preference/abstinence behaviors. As brain incorporation of trans and n-6 PUFA modifies its physiological functions, it may facilitate drug addiction.     

依达拉奉对慢性缺血致血管性痴呆大鼠行为学及形态学的影响

目的观察依达拉奉对慢性缺血致血管性痴呆(VD)大鼠行为学及形态学的影响,探讨依达拉奉在治疗VD中的应用价值。方法实验分假手术组、模型组及都可喜对照组及依达拉奉治疗组,应用双侧颈总动脉结扎方法制备慢性脑缺血大鼠痴呆模型,观察各组大鼠的记忆功能及脑组织超微结构改变。结果缺血组水迷宫表现同对照组、都可喜组及依达拉奉组相比有显著差异(P<0.05),依达拉奉组与都可喜组相比未见显著差异。同时电镜观察结果也发现依达拉奉组及都可喜组与模型组及假手术组相比神经细胞病理改变较轻,且依达拉奉组线粒体及前膜突触小泡增多,代谢活动较都可喜组旺盛。结论依达拉奉可能通过减轻海马神经元的损伤来改善慢性脑缺血大鼠空间学习记忆障碍,证明依达拉奉对慢性缺血致VD大鼠具有治疗作用。     

Age-related changes in rostral basal forebrain cholinergic and GABAergic projection neurons: relationship with spatial impairment

Both cholinergic and GABAergic projections from the rostral basal forebrain contribute to hippocampal function and mnemonic abilities. While dysfunction of cholinergic neurons has been heavily implicated in age-related memory decline, significantly less is known regarding how age-related changes in codistributed GABAergic projection neurons contribute to a decline in hippocampal-dependent spatial learning. In the current study, confocal stereology was used to quantify cholinergic (choline acetyltransferase [ChAT] immunopositive) neurons, GABAergic projection (glutamic decarboxylase 67 [GAD67] immunopositive) neurons, and total (neuronal nuclei [NeuN] immunopositive) neurons in the rostral basal forebrain of young and aged rats that were first characterized on a spatial learning task. ChAT immunopositive neurons were significantly but modestly reduced in aged rats. Although ChAT immunopositive neuron number was strongly correlated with spatial learning abilities among young rats, the reduction of ChAT immunopositive neurons was not associated with impaired spatial learning in aged rats. In contrast, the number of GAD67 immunopositive neurons was robustly and selectively elevated in aged rats that exhibited impaired spatial learning. Interestingly, the total number of rostral basal forebrain neurons was comparable in young and aged rats, regardless of their cognitive status. These data demonstrate differential effects of age on phenotypically distinct rostral basal forebrain projection neurons, and implicate dysregulated cholinergic and GABAergic septohippocampal circuitry in age-related mnemonic decline.     

敲除淀粉样前体蛋白基因促进铝诱导的小鼠认知障碍损伤

目的 淀粉样前体蛋白(APP)基因是与痴呆症发生发展相关的重要基因,利用APP基因敲除小鼠探讨铝诱导的认知障碍损伤,及APP对中
毒性认知障碍损伤的作用。方法 3月龄同窝阴性小鼠分为野生对照组（WT）和铝处理组（WT+Al）,APP敲除小鼠分为模型对照组（APP^-/- ）和
模型处理组（APP^-/- +Al）,每组10只。铝处理组在粮食中加入相应剂量的乳酸铝,同窝阴性小鼠和APP^-/-小鼠给予常规鼠粮作为对照,乳酸
铝处理8周后进行水迷宫实验。HE染色观察小鼠脑组织神经病理改变;Western blotting检测糖原合成激酶3β(GSK-3β)和Caspase-3的活性变
化。结果 与WT相比,WT+Al小鼠在原平台区域停留时间和穿越原平台区域次数减少了28.1%和18.8%,而APP^-/- +Al小鼠在原平台区域停留时间
和穿越原平台区域次数减少了44.1%和51%。Western blotting显示,WT+Al小鼠和APP^-/-+Al小鼠脑组织中p-GSK-3β分别减少了17.4%和46.4%。结论 APP基因敲除促进铝诱导的神经毒性和学习记忆损伤。APP基因敲除导致GSK-3β的磷酸化水平降低、活性增高。由于GSK-3β活性增加对痴呆症具有促进作用,推测APP通过抑制GSK-3β活性在痴呆症发生过程中发挥保护效应。     

运动疲劳导致大鼠焦虑并伴有海马CA1区θ节律活动增强

目的:研究运动疲劳对大鼠焦虑情绪的影响,观测海马CA1区场电位θ节律震荡的变化,揭示运动疲劳引发不良情绪效应的可能神经电生理机制。方法:雄性Wistar大鼠随机分为对照组(control)和运动疲劳组(exercise training,ET),采用反复7 d力竭跑台训练方式建立疲劳模型。行为学实验采用高架十字迷宫观察大鼠焦虑行为的改变。随后,利用在体电生理记录方法,比较两组大鼠海马局部场电位θ节律活动的差异。结果:高架十字迷宫检测发现,ET组大鼠进入高架十字迷宫开放臂次数较对照组大鼠明显减少(P<0.05),并且在其中停留的时间也显著性缩短(P<0.01);同时,在闭合臂的活动时间大幅延长(P<0.01)。在体海马CA1区θ节律电信号记录显示,ET组大鼠功率峰值显著高于对照组大鼠(P<0.05),而功率峰值对应的θ节律频率值不存在组间差异(P>0.05)。结论:运动疲劳后大鼠探索行为减少,焦虑样行为增多,并伴有海马CA1区θ节律活动增强。这种焦虑情绪与θ节律震荡活动的改变相关,提示θ节律场电位信号活动的增强,可能是运动疲劳导致焦虑等不良情绪产生的电生理机制之一。     

Moderate early life stress improves adult zebrafish (Danio rerio) working memory but does not affect social and anxiety‐like responses

Early life stress (ELS) is defined as a short or chronic period of trauma, environmental or social deprivation, which can affect different neurochemical and behavioral patterns during adulthood. Zebrafish (Danio rerio) have been widely used as a model system to understand human neurodevelopmental disorders and display translationally relevant behavioral and stress‐regulating systems. In this study, we aimed to investigate the effects of moderate ELS by exposing young animals (6‐weeks postfertilization), for 3 consecutive days, to three stressors, and analyzing the impact of this on adult zebrafish behavior (16‐week postfertilization). The ELS impact in adults was assessed through analysis of performance on tests of unconditioned memory (free movement pattern Y‐maze test), exploratory and anxiety‐related task (novel tank diving test), and social cohesion (shoaling test). Here, we show for the first time that moderate ELS increases the number of alternations in turn‐direction compared to repetitions in the unconditioned Y‐maze task, suggesting increased working memory, but has no effect on shoal cohesion, locomotor profile, or anxiety‐like behavior. Overall, our data suggest that moderate ELS may be linked to adaptive flexibility which contributes to build “resilience” in adult zebrafish by improving working memory performance.