Biochem Biophys Res Commun. 2025 Sep 25;785:152670. doi: 10.1016/j.bbrc.2025.152670. Online ahead of print.
ABSTRACT
OBJECTIVE: This study aims to elucidate the molecular mechanisms by which Arsenic (As) exposure induces abnormal fetal brain neural development and subsequent anxiety- and depression-like behaviors (ADB) through non-coding RNA (ncRNA), providing a new theoretical basis for the prevention and treatment of related diseases.
METHODS: This study established a mouse model of in utero arsenic exposure by administering a 0.5 mg/kg sodium arsenite solution to pregnant mice, and evaluated the ADB in mice through neurobehavioral tests, tissue analysis, and histopathological assessments.
RESULTS: In utero arsenic exposure (IAsE) mice exhibited pronounced ADB, oxidative stress, and neuronal damage in the hippocampus. The activity of Superoxide Dismutase (SOD) in the hippocampus was significantly decreased, while the level of Malondialdehyde (MDA) was significantly increased (P < 0.001).The expressions of c-Fos and Bax were elevated (P < 0.05), Nrf2 and Bcl-2 expression was decreased (P < 0.0001). Additionally, the number of hippocampal neurons decreased and their structure was disorganized. Moreover, transcriptomic sequencing revealed significant differential expression of messenger RNA (mRNA), circular RNA (circRNA), and microRNA (miRNA) in the brain tissues of IAsE mice, leading to the construction of a competing endogenous RNA network (ceRNA) network based on differentially expressed genes (DEGs). Enrichment analysis indicated that these DEGs were primarily involved in biological processes such as oxidative stress, cell apoptosis, and nervous system development.
CONCLUSION: The study demonstrates that IAsE disrupts the ceRNA regulatory network in brain tissues, unbalances oxidative stress, causes abnormal neuronal activation and apoptosis, ultimately impairing hippocampal function and triggering ADB.
PMID:41016333 | DOI:10.1016/j.bbrc.2025.152670
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