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早期母婴分离会损害成年雄性大鼠的学习和记忆能力,并改变其海马体的基因表达。

Early maternal deprivation impairs learning and memory and alters hippocampal gene expression in adult male rats.

机构信息

Department of Cell Biology and Genetics, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an 710061, PR China; National Local Joint Engineering Research Center of Biodiagnostics and Biotherapy, The Second Affiliated Hospital of Xian Jiaotong University, Xi'an 710061, PR China.

Department of Cell Biology and Genetics, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an 710061, PR China; Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education of China, Xi'an Jiaotong University, Xi'an 710061, PR China.

出版信息

Neurobiol Learn Mem. 2021 Sep;183:107479. doi: 10.1016/j.nlm.2021.107479. Epub 2021 Jun 11.

DOI:10.1016/j.nlm.2021.107479
PMID:34119613
Abstract

Maternal deprivation (MD) in early life severely disrupts hippocampal development, leading to persistent cognitive and behavior deficits. The current study uncovered that early MD (P1-P21) impaired spatial learning and memory capacity detected by Morris water maze (MWM) tests from juvenile (P31) to adult (P81) rats compared to age-matched controls. And the protein expression in hippocampus were detected by two-dimensional gel electrophoresis (2-DE) before MWM, respectively. Protein changes in hippocampal were examined to identify the molecular pathways underlying MD-induced hippocampal dysfunction. There were 11 differentially expressed proteins analyzed between adult MD and control male rats, while the 8 proteins were then identified by UPLC-ESI-Q-TOF-MS. Gene Ontology (GO) annotations of the identified proteins were related to neuronal and glial cytoskeletal dynamics, membrane signaling, stress responses, biosynthesis, and metabolism. The different expression proteins spectrin alpha chain, non-erythrocytic 1 (Sptan1), ATP-citrate synthase (Acly), and heat shock protein 90-alpha (Hsp90aa1) have been verified by western blot analysis, and their expression levels showed consistent with 2-DE analysis. In addition, glial fibrillary acidic protein (GFAP) was also found reduced in adult hippocampus of MD rats. This study identifies candidate proteins encompassing a range of functional categories that may contribute to persistent learning and memory deficits due to early life MD.

摘要

早期生活中的母婴分离(MD)严重破坏海马体发育,导致持续的认知和行为缺陷。本研究发现,与年龄匹配的对照组相比,早期 MD(P1-P21)在幼鼠(P31)到成年(P81)大鼠的水迷宫(MWM)测试中损害了空间学习和记忆能力。在进行 MWM 之前,通过二维凝胶电泳(2-DE)分别检测海马体中的蛋白质表达。检查海马体中的蛋白质变化,以确定 MD 诱导的海马功能障碍的分子途径。在成年 MD 和对照雄性大鼠之间分析了 11 种差异表达的蛋白质,然后通过 UPLC-ESI-Q-TOF-MS 鉴定了 8 种蛋白质。鉴定出的蛋白质的基因本体(GO)注释与神经元和神经胶质细胞细胞骨架动力学、膜信号转导、应激反应、生物合成和代谢有关。差异表达蛋白血影蛋白α链、非红细胞 1(Sptan1)、三磷酸腺苷柠檬酸合酶(Acly)和热休克蛋白 90-α(Hsp90aa1)已通过 Western blot 分析验证,其表达水平与 2-DE 分析一致。此外,还发现 MD 大鼠成年海马体中的神经胶质纤维酸性蛋白(GFAP)减少。这项研究确定了候选蛋白,涵盖了一系列功能类别,这些蛋白可能导致早期生活 MD 引起的持续学习和记忆缺陷。

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