Whole-transcriptome analysis of aluminum-exposed rat hippocampus and identification of ceRNA networks to investigate neurotoxicity of Al.

Abstract

Aluminum is a known neurotoxin that can induce Aβ deposition and abnormal phosphorylation of tau protein, leading to Alzheimer disease (AD)-like damages such as neuronal damage and decreased learning and memory functions. In this study, we constructed a rat model of subchronic aluminum maltol exposure, and the whole-transcriptome sequencing was performed on the hippocampus of the control group and the middle-dose group. A total of 167 miRNAs, 37 lncRNAs, 256 mRNAs, and 64 circRNAs expression changed. The Kyoto Encyclopedia of Genes and Genomes showed that PI3K/AKT pathway was the most enriched pathway of DEGs, and IRS1 was the core molecule in the PPI network. circRNA/lncRNA-miRNA-mRNA networks of all DEGs, DEGs in the PI3K/AKT pathway, and IRS1 were constructed by Cytoscape. Molecular experiment results showed that aluminum inhibited the IRS1/PI3K/AKT pathway and increased the content of Aβ and tau. In addition, we also constructed an AAV intervention rat model, proving that inhibition of miR-96-5p expression might resist aluminum-induced injury by upregulating expression of IRS1. In general, these results suggest that the ceRNA networks are involved in the neurotoxic process of aluminum, providing a new strategy for studying the toxicity mechanism of aluminum and finding biological targets for the prevention and treatment of AD.

• Authors: Chanting He, Xiaoyan Zhao, Yang Lei, Jisheng Nie, Xiaoting Lu, Jing Song, Linping Wang, Huan Li, Fangqu Liu, Yidan Zhang, Qiao Niu
• Journal: Molecular therapy. Nucleic acids (Mol Ther Nucleic Acids) Vol. 26 Pg. 1401-1417 (Dec 03 2021) ISSN: 2162-2531 [Print] United States
• PMID: 34900398 (Publication Type: Journal Article)
• Copyright: © 2021 The Author(s).