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铝诱导大鼠海马损伤的全蛋白质组学特征:低剂量的铝真的安全吗?

Global Proteomic Profile of Aluminum-Induced Hippocampal Impairments in Rats: Are Low Doses of Aluminum Really Safe?

机构信息

Laboratory of Functional and Structural Biology, Institute of Biological Sciences, Federal University of Pará, Belém 66075110, Brazil.

Graduate Program in Health and Society, Faculty of Health Sciences, State University of Rio Grande do Norte (UERN), Mossoro 59610210, Brazil.

出版信息

Int J Mol Sci. 2022 Oct 19;23(20):12523. doi: 10.3390/ijms232012523.

Abstract

Hippocampus is the brain area where aluminum (Al) accumulates in abundance and is widely associated with learning and memory. In the present study, we evaluate behavioral, tissue, and proteomic changes in the hippocampus of Wistar rats caused by exposure to doses that mimic human consumption of aluminum chloride (AlCl) in urban areas. For this, male Wistar rats were divided into two groups: Control (distilled water) and AlCl (8.3 mg/kg/day), both groups were exposed orally for 60 days. After the Al exposure protocol, cognitive functions were assessed by the Water maze test, followed by a collection for analysis of the global proteomic profile of the hippocampus by mass spectrometry. Aside from proteomic analysis, we performed a histological analysis of the hippocampus, to the determination of cell body density by cresyl violet staining in fields (CA) 1 and 3, and hilus regions. Our results indicated that exposure to low doses of aluminum chloride triggered a decreased cognitive performance in learning and memory, being associated with the deregulation of proteins expression, mainly those related to the regulation of the cytoskeleton, cellular metabolism, mitochondrial activity, redox regulation, nervous system regulation, and synaptic signaling, reduced cell body density in CA1, CA3, and hilus.

摘要

海马体是大脑中铝(Al)大量积累的区域,与学习和记忆广泛相关。在本研究中,我们评估了暴露于模拟城市地区人类摄入氯化铝(AlCl)剂量的 Wistar 大鼠海马体的行为、组织和蛋白质组变化。为此,雄性 Wistar 大鼠分为两组:对照组(蒸馏水)和 AlCl 组(8.3mg/kg/天),两组均经口暴露 60 天。在 Al 暴露方案后,通过水迷宫测试评估认知功能,然后通过质谱法对海马体的全蛋白质组谱进行分析。除蛋白质组分析外,我们还对海马体进行了组织学分析,通过 Cresyl 紫染色测定 CA1 和 CA3 及门区的细胞体密度。我们的结果表明,低剂量氯化铝暴露会导致学习和记忆认知能力下降,这与蛋白质表达失调有关,主要与细胞骨架调节、细胞代谢、线粒体活性、氧化还原调节、神经系统调节和突触信号转导有关,CA1、CA3 和门区的细胞体密度降低。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2ef/9603961/a4ea7b820256/ijms-23-12523-g001a.jpg

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