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Amyloid-beta (1-42) lesion of CA1 rat dorsal hippocampus reduces contextual fear memory and increases expression of microglial genes regulating neuroinflammation.
Behavioural Brain Research ( IF 2.7 ) Pub Date : 2020-06-30 , DOI: 10.1016/j.bbr.2020.112795
Oluwadamilola F Shallie 1 , Musa V Mabandla 1
Affiliation  

Emerging evidence indicates that the pathogenesis of Alzheimer’s disease (AD) is not confined to neuronal disruptions but robustly communicates with the brain’s immune system. Genome-wide analysis suggests that several genes, which increase the risk for AD, encode for factors that regulate the glial clearance of misfolded proteins and the inflammatory reaction. This study reappraises the amyloid hypothesis by focusing on the impact of neuroinflammation in a beta-amyloid model of AD, how this possibly exacerbates the disease's progression, and the correlation between genes regulating neuroinflammation (CD33 and TREM2) with post-training recall. Male Sprague-Dawley rats were used for this study, randomly divided into a vehicle group of rats (n = 40) that were infused with phosphate-buffered saline (PBS) and an Aβ(1–42) group (n = 40) that were infused with the neurotoxin Aβ(1–42) peptide. Fear conditioning test (FCT) to assess fear memory was conducted pre and post-lesion. The polymerase chain reaction was performed to determine the expression levels of CD33 and TREM2 genes. Our results show that Aβ(1–42) lesion of the rat CA1 hippocampal subregion significantly reduces contextual fear memory, and this reduction was exacerbated as the post-lesion days increased. We also observed an increase in the expression levels of CD33 and TREM2 genes in the Aβ(1–42) lesioned groups compared to their corresponding vehicle groups. Taken together, the behavioral and gene expression data provide inferential evidence that Aβ(1–42) infusion impairs contextual memory by disrupting cellular pattern separation processes in the hippocampus, thus linking neuroinflammation to specific neural circuit disruption and cognitive deficit.



中文翻译:

CA1 大鼠背侧海马的淀粉样蛋白-β (1-42) 损伤减少了情境恐惧记忆并增加了调节神经炎症的小胶质细胞基因的表达。

新出现的证据表明,阿尔茨海默病 (AD) 的发病机制不仅限于神经元破坏,还与大脑的免疫系统密切相关。全基因组分析表明,几个增加 AD 风险的基因编码调节错误折叠蛋白的胶质清除和炎症反应的因子。本研究通过关注神经炎症对 AD β-淀粉样蛋白模型的影响、这可能如何加剧疾病的进展以及调节神经炎症的基因(CD33 和 TREM2)与训练后回忆之间的相关性,重新评估了淀粉样蛋白假说。本研究使用雄性 Sprague-Dawley 大鼠,随机分为一组大鼠(n = 40),分别注入磷酸盐缓冲盐水 (PBS) 和 Aβ (1-42)注入神经毒素 Aβ (1-42)肽的组(n = 40)。评估恐惧记忆的恐惧条件测试(FCT)在损伤前和损伤后进行。进行聚合酶链反应以确定 CD33 和 TREM2 基因的表达水平。我们的结果表明,大鼠 CA1海马亚区的(1-42)损伤显着降低了情境恐惧记忆,并且随着损伤后天数的增加,这种减少会加剧。我们还观察到 Aβ (1-42)损伤组中 CD33 和 TREM2 基因的表达水平与其相应的载体组相比有所增加。总之,行为和基因表达数据提供了 Aβ (1-42) 输注通过破坏海马中的细胞模式分离过程来损害上下文记忆,从而将神经炎症与特定的神经回路破坏和认知缺陷联系起来。

更新日期:2020-07-09
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