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ORIGINAL RESEARCH article

Front. Pharmacol.
Sec. Experimental Pharmacology and Drug Discovery
Volume 15 - 2024 | doi: 10.3389/fphar.2024.1440515
This article is part of the Research Topic Commercialization and Industrialization in Experimental Pharmacology and Drug Discovery: 2023 View all 5 articles

Transcriptome analysis of aged SAMP8 mouse model of Alzheimer's disease reveals novel molecular targets of Formononetin protection

Provisionally accepted
Bo Liu Bo Liu 1,2*Jie Liu Jie Liu 2Jing-Shan Shi Jing-Shan Shi 2
  • 1 Zunyi Medical University, Zunyi, China
  • 2 Key Laboratory of Basic Pharmacology of Ministry of Education, Zunyi Medical University, Zunyi, Guizhou Province, China

The final, formatted version of the article will be published soon.

    Background: Senescence accelerated mouse prone 8 (SAMP8) and age-matched SAMR1 mice are used to study the pathogenesis and therapeutics of Alzheimer's disease (AD), however, the molecular mechanisms are not completely understood. Objective: This study aimed to examine the effects of 5-month administration of Formononetin in SAMP8 mice and used RNA-Seq to explore the molecular targets. Methods: SAMP8 mice were orally given Formononetin (0, 8 and 16 mg/kg) from 4 months of age, and age-matched SAMR1 mice were used as controls.Behavioral tests were performed in 9-month-old mice, followed by histopathology. Total RNA from hippocampus was isolated and subjected to RNA-Seq, RT-qPCR, and bioinformatics analysis.: The 9-month-old SAMP8 mice exhibited cognition deficits evidenced by Novel object recognition, Open field test, Elevated plus maze and Passive avoidance. Nissl bodies in the cortex and hippocampus were decreased. Formononetin treatments ameliorated behavioral deficits and improved morphological changes, which were evidenced by Nissl and H&E staining. RNA-Seq revealed distinct gene expression pattern between SAMP8 and SAMR1 mice. Differentially expressed genes in SAMP8 mice were attenuated or normalized by Formononetin. Ingenuity pathway analysis of Canonical pathway and Upstream regulators revealed increases in proinflammatory factors, immune dysfunction and decreases in NRF2 and SIRT-1 signaling pathways, leading to neuroinflammation. Formononetin treatment attenuated or reversed these molecular changes. The transcriptome of SAMP8 mice was correlated with transcriptome profiles of other AD mouse models in GEO database. Conclusion: Neuroinflammation and decreased antioxidative and SIRT-1 signaling contributed to cognitive deficit in aged SAMP8 mice, which are potential therapeutic targets of Formononetin in combination with other therapies.

    Keywords: RNA-seq analysis, aged SAMP8 mouse, Alzheimer's disease, Formononetin, Ingenuity Pathway Analysis

    Received: 29 May 2024; Accepted: 26 Jul 2024.

    Copyright: © 2024 Liu, Liu and Shi. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Bo Liu, Zunyi Medical University, Zunyi, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.