Transcriptomic Analyses of Exercise Training in Alzheimer’s Disease Cerebral Cortex

Article type: Research Article

Authors: Widjaya, Michael Anekson^a | Cheng, Yu-Jung^b | Kuo, Yu-Min^c | Liu, Chia-Hsin^d | Cheng, Wei-Chung^{d; e; *} | Lee, Shin-Da^{b; f; *}

Affiliations: [a] Graduate Institute of Biomedical Sciences, College of Medicine, China Medical University, Taichung, Taiwan | [b] Department of Physical Therapy, Graduate Institute of Rehabilitation Science, China Medical University, Taichung, Taiwan | [c] Department of Cell Biology and Anatomy, Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung, Tainan, Taiwan | [d] Research Center for Cancer Biology, China Medical University, Taichung, Taiwan | [e] Ph.D. Program for Cancer Biology and Drug Discovery, China Medical University and Academia Sinica, Taiwan | [f] School of Rehabilitation Medicine, Weifang Medical University, Weifang, China

Correspondence: [*] Correspondence to: Wei-Chung Cheng, 8F, No. 6, Hsueh-Shih Road, Taichung 404, Taiwan. Tel.: +886 4 22052121/Ext. 7820; E-mail: heng@mail.cmu.edu.tw and Shin-Da Lee, No. 100, Sec. 1, Jingmao Rd., Beitun Dist., Taichung 406040, Taiwan. Tel.: +886 4 22053366/Ext. 7300; E-mail: shinda@mail.cmu.edu.tw.

Abstract: Background:Research reported exercise could reduce Alzheimer’s disease (AD) symptoms in human and animals. However, the molecular mechanism of exercise training via transcriptomic analysis was unclear especially in AD in the cortex area. Objective:Investigate potential significant pathways in the cortex area that were affected by exercise during AD. Methods:RNA-seq analysis, differential expressed genes, functional enrichment analysis, and GSOAP clustering analysis were performed in the isolated cerebral cortex from eight 3xTg AD mice (12 weeks old) randomly and equally divided into control (AD) and exercise training (AD-EX) group. Swimming exercise training in AD-EX group was conducted 30 min/day for 1 month. Results:There were 412 genes significant differentially expressed in AD-EX group compared to AD group. Top 10 upregulated genes in AD-EX group against AD group mostly correlated with neuroinflammation, while top 10 downregulated genes mostly had connection with vascularization, membrane transport, learning memory, and chemokine signal. Pathway analysis revealed the upregulated interferon alpha beta signaling in AD-EX had association with cytokines delivery in microglia cells compared to AD and top 10 upregulated genes involved in interferon alpha beta were Usp18, Isg15, Mx1, Mx2, Stat1, Oas1a, and Irf9; The downregulated extracellular matrix organization in AD-EX had correlation with Aβ and neuron cells interaction and Vtn was one of the top 10 downregulated genes involved in this pathway. Conclusion:Exercise training influenced 3xTg mice cortex through interferon alpha beta signaling upregulation and extracellular matrix organization downregulation based on transcriptomics analysis.

Keywords: Alzheimer’s disease, bioinformatics, cortex, exercise

DOI: 10.3233/JAD-221139

Journal: Journal of Alzheimer's Disease, vol. 93, no. 1, pp. 349-363, 2023