Work

Hippocampal Senescence-Like Alterations in a Maternal Deprivation Model: Integrative Identification of Candidate Genomic Instability and Epigenetic Pathways

Year: 2026

Type: article

Abstract: Autism spectrum disorder (ASD) is a complex neurodevelopmental condition with incompletely understood biological mechanisms. Whether neurocognitive impairment in ASD is associated with hippocampal neuronal senescence (neurescence) remains unclear. In this study, we employed a maternal deprivation (MD) rat model to investigate ASD-like behavioral alterations and hippocampal neuronal senescence. Behavioral phenotyping demonstrated alterations in social and repetitive behaviors, together with a numerical reduction in object recognition performance that did not reach conventional statistical significance. Senescence-associated β-galactosidase (SA-β-gal) staining and cell-cycle analysis revealed increased cellular senescence accompanied by significant G1-phase arrest in hippocampal neurons. To identify molecular pathways associated with these changes, we performed an integrative reanalysis of six publicly available microarray datasets (with a seventh accession, GSE111176, retained as a hierarchical SuperSeries) derived from iPSC-derived neurons, peripheral blood, gastrointestinal tissue, and an in vitro neuronal-differentiation model. This analysis identified seven candidate genes, TP53 , PPARGC1A , ERCC1 , ERCC4 , DNMT1 , SUV39H1 , and KAT2A , involved in DNA repair, epigenetic regulation, and mitochondrial homeostasis, and their altered expression was validated by RT-qPCR in hippocampal tissues from the MD model. Together, the findings identify hippocampal senescence-like alterations in the maternal-deprivation model and highlight candidate genomic-instability and epigenetic pathways that may be relevant to neurodevelopmental phenotypes associated with ASD.

Source: Cellular and Molecular Neurobiology

DOI: 10.1007/s10571-026-01848-x