氟西汀对癫痫合并抑郁大鼠海马GFAP、NeuN表达的影响

目的探讨氟西汀对癫痫合并抑郁大鼠海马齿状回胶质纤维酸性蛋白(GFAP)、神经元核抗原(NeuN)表达的影响。方法SPF级SD大鼠60只,随机分为对照组、模型组、氟西汀低、中、高剂量组各12只。模型组和对照组给予等剂量生理盐水,1次/d,腹腔注射;氟西汀低、中、高剂量组给予氟西汀(5.0、7.5、10.0 mg/kg),1次/d,腹腔注射。治疗28 d,采用强迫游泳实验和旷场实验测试大鼠行为学表现,采用免疫组化、RT-PCR检测海马GFAP、NeuN表达。结果造模后,与对照组相比,模型组、氟西汀低、中、高剂量组不动时间延长,垂直运动次数、水平运动次数明显下降(P<0.05)。干预后,模型组不动时间明显长于对照组,垂直运动次数、水平运动次数明显低于对照组(P<0.01);与模型组相比,氟西汀低、中、高剂量组不动时间缩短,垂直运动次数、水平运动次数明显增加(P<0.05);尤其是氟西汀高剂量组,较氟西汀低、中剂量组相比有统计学意义(P<0.05)。免疫组化、RT-PCR显示,与对照组相比,模型组GFAP表达明显增加、NeuN表达明显下降(P<0.05);与模型组相比,氟西汀低、中、高剂量组GFAP表达明显下降、NeuN表达明显增加(P<0.05);尤其是氟西汀高剂量组,较氟西汀低、中剂量组相比有统计学意义(P<0.05)。结论氟西汀可能通过改变海马区GFAP、NeuN表达,并呈剂量依赖性,发挥神经保护作用,改善癫痫合并抑郁大鼠抑郁症状。     

Nobiletin对慢性低灌注损伤后小鼠脑海马神经血管单元的影响

目的观察川陈皮素(NOB)对小鼠慢性脑低灌注(CCH)模型海马区神经血管单元各主要组分的保护作用。方法昆明小鼠随机分为对照组、模型组和NOB高、低剂量处理组各10只,模型组和NOB处理组进行双侧颈总动脉结扎,对照组不结扎。术后2 w进行旷场实验及Y迷宫检测学习记忆功能,Western印迹法测定小鼠海马区神经元生长相关蛋白(GAP)-43、突触素(SYN)、水通道蛋白(AQP)4表达,检测海马神经细胞可塑性及血脑屏障功能。结果与模型组相比,NOB处理组自由活动无显著差异,其中高剂量组探索能力显著增强,逃避潜伏期显著减短(P<0.05);NOB处理组均显著增加海马区GAP-43、SYN、AQP4及Claudin-5表达(P<0.05)。结论NOB可通过对海马的神经血管单元各组分的保护作用,改善CCH所致小鼠学习记忆功能受损。     

Alterations in Brain Polyribosomal RNA Translation and Lymphocyte Proliferation in Prenatal Ethanol-Exposed Rats

The long-term effects of prenatal ethanol exposure on the properties of brain polysomes and the proliferative responses of lymphocytes to mitogenic stimulation in adult offspring were assessed. Female Sprague-Dawley rats either ingested the control or 6.6% ethanol-containing Lieber-DeCarli liquid diet during the 3rd trimester of pregnancy. Controls were age-matched and pair-fed. At 42 to 72 days of age, ethanol effects were evaluated on the (1) polysomal properties in the cerebral hemispheres, cerebellum, and hippocampal regions of the brain after translation in a messenger RNA (mRNA)-dependent rabbit reticulocyte lysate system and (2) immunologic functions of lymphocytes cultured from spleen cells by measuring their responses to mitogenic stimulation. Results showed long-term adverse effects of in utero ethanol exposure on the polysomal RNA translation in each of the three brain regions tested with free polysomal mRNAs affected more than the bound polysomal mRNAs. Of these, the hippocampal region appeared to sustain the most injurious effects. In addition, a suppression of the mitogen-induced lymphocyte proliferative responses were present under these conditions. The degree of suppression varied with the specific mitogen used. Data suggest that the ethanol effects on the CNS and lymphocyte proliferation are most possibly irreversible, and in the case of the CNS, a post-translational modification by ethanol is indicated. The reduced lymphocyte responses are suggestive of a possible interference by ethanol of the synthesis of interleukin-2 (IL-2) and/or a reduced binding of IL-2 with its receptor (IL-2 receptors).     

Induction of heat shock protein 70 and glial fibrillary acidic protein in the postischemic gerbil hippocampus

Immunohistochemical changes of heat shock protein 70 (HSP 70) and glial fibrillary acidic protein (GFAP) were investigated in the gerbil hippocampus 1 h-7 days after 10 min of cerebral ischemia. Transient cerebral ischemia caused HSP 70 expression in GFAP-positive astrocytes in a delayed fashion, as compared with a rapid induction in vulnerable neurons such as hilar neurons. The present results may offer clues to elucidate the mechanisms of ischemic neuronal damage.     

Chronic Oral Administration of Magnesium-L-Threonate Prevents Oxaliplatin-Induced Memory and Emotional Deficits by Normalization of TNF-α/NF-κB Signaling in Rats

Antineoplastic drugs such as oxaliplatin (OXA) often induce memory and emotional deficits. At present, the mechanisms underlying these side-effects are not fully understood, and no effective treatment is available. Here, we show that the short-term memory deficits and anxiety-like and depression-like behaviors induced by intraperitoneal injections of OXA (4 mg/kg per day for 5 consecutive days) were accompanied by synaptic dysfunction and downregulation of the NR2B subunit of N-methyl-D-aspartate receptors in the hippocampus, which is critically involved in memory and emotion. The OXA-induced behavioral and synaptic changes were prevented by chronic oral administration of magnesium-L-threonate (L-TAMS, 604 mg/kg per day, from 2 days before until the end of experiments). We found that OXA injections significantly reduced the free Mg²⁺ in serum and cerebrospinal fluid (from ~ 0.8 mmol/L to ~ 0.6 mmol/L). The Mg²⁺ deficiency (0.6 mmol/L) upregulated tumor necrosis factor (TNF-α) and phospho-p65 (p-p65), an active form of nuclear factor-kappaB (NF-κB), and downregulated the NR2B subunit in cultured hippocampal slices. Oral L-TAMS prevented the OXA-induced upregulation of TNF-α and p-p65, as well as microglial activation in the hippocampus and the medial prefrontal cortex. Finally, similar to oral L-TAMS, intracerebroventricular injection of PDTC, an NF-κB inhibitor, also prevented the OXA-induced memory/emotional deficits and the changes in TNF-α, p-p65, and microglia. Taken together, the activation of TNF–α/NF–κB signaling resulting from reduced brain Mg²⁺ is responsible for the memory/emotional deficits induced by OXA. Chronic oral L-TAMS may be a novel approach to treating chemotherapy-induced memory/emotional deficits.Electronic supplementary materialThe online version of this article (10.1007/s12264-020-00563-x) contains supplementary material, which is available to authorized users.     

伽玛刀对大鼠海马体内体外放射生物学作用

目的 探讨伽玛刀照射对大鼠海马组织与培养的海马神经元放射生物学作用的差异.方法 分别对大鼠海马组织和堵养的海马神经元进行伽玛刀照射,观察照射前后组织超微结构变化、FOS和HSP70表达以及细胞存活情况.结果 在体海马组织和培养的海马神经元对放射反应不同.高剂量(150和100Gy)引起在体海马组织严重损伤,60Gy引起轻度损伤,而低剂量(30Gy)即可引起培养的海马神经损伤和死亡.大鼠海马组织和培养的海马神经元的FOS和HSP70表达与照射强度和照射后时间有关.结论 海马组织和培养的海马神经细胞的损伤程度都与伽玛刀的照射强度存在明显的剂量-效应关系和时间-效应关系,但两者对伽玛射线的反应存在一定差异.     

APOE-ε4 associates with hippocampal volume,learning, and memory across the spectrum of Alzheimer's disease and dementia with Lewy bodies

Introduction

Although the apolipoprotein E ε4-allele (APOE-ε4) is a susceptibility factor for Alzheimer's disease (AD) and dementia with Lewy bodies (DLB), its relationship with imaging and cognitive measures across the AD/DLB spectrum remains unexplored.

高脂饮食对载脂蛋白E基因敲除小鼠海马CA_3区形态学变化及mortalin蛋白表达的影响

目的 观察载脂蛋白E(apolipoprotein E,ApoE)基因敲除(knock-out,KO)及高脂饮食后小鼠海马CA_3区形态学及mortalin蛋白表达的变化,以探讨这些因素与记忆损伤及阿尔茨海默病的关系.方法 10只野生型小鼠予普通饲料喂养作为对照(C)组,10只ApoE KO小鼠予普通饲料喂养作为KO组,10只ApoE KO小鼠予高脂饲料喂养作为KO-HF组.小鼠3个月龄成模后,称重;取血检测血脂;取小鼠脑组织分别进行HE染色、尼氏染色、神经原纤维银染、免疫组织化学染色和计算机图像分析.结果 KO组体质鼍、总胆固醇、甘油三酯及低密度脂蛋白胆固醇含量与C组相比明显升高,KO-HF组升高更明显;KO组(0.301±0.031)及KO-HF组(0.261±0.020)尼氏体较C组(0.341±0.035)减少(F=18.068,P<0.05);KO组(0.322±0.060)及KO-HF组(0.391±0.041)mortalin表达较C组(0.256±0.061)升高(F=15.230,P<0.05);KO组及KO-HF组未见明显神经原纤维缠结.结论 ApoE KO及高脂饮食可致小鼠海马CA,区锥体细胞内尼氏体减少,mortalin表达升高,该蛋白的异常表达可能与阿尔茨海默病的发病相关.     

慢性铝暴露对大鼠海马神经元中toll样受体4蛋白及其mRNA表达的影响

目的 通过研究铝暴露对介导天然免疫的关键蛋白toll样受体(TLR)的影响,探讨慢性铝暴露诱导学习记忆损伤的潜在机制.方法 取80只断乳后Wistar大鼠,随机分为4组,每组20只;其中1组为对照组(用蒸馏水喂养),其他3组为铝暴露组,分别用含0.2%、0.4%和0.6%浓度的AlCl_3蒸馏水喂养3个月.免疫印迹(Western blot)方法检测各组大鼠海马中TLR4的蛋白表达情况;逆转录-聚合酶链反应(RT-PCR)方法检测各组大鼠海马中TLR4 mRNA的表达情况.结果 铝暴露组大鼠的学习记忆能力下降;与对照组(0.91±0.14)相比,0.2%、0.4%和0.6%浓度的铝暴露各组海马组织TLR4的蛋白表达(0.95±0.15、1.44±0.22、2.03±0.28)显著增高(F=37.575,P<0.05);与对照组(0.59±0.06)相比,铝暴露各组TLR4 mRNA的表达(0.86±0.04、0.95±0.04、1.06±0.09)显著增高(F=65.474,P<0.05).结论 慢性铝暴露损伤大鼠的学习记忆能力可能与上调TLR4蛋白及其mRNA的表达相关.