ABSTRACT NUMBER: ESOC2026A902 MECHANISM OF TRANSCRIPTION FACTOR MAF1 REGULATING SYNAPTIC PLASTICITY ON POST STROKE COGNITIVE IMPAIRMENT

Abstract Background and aims Post stroke cognitive impairment (PSCI) is the most common complication in patients with ischemic stroke and the pathogenic mechanism is still unclear. Synaptic plasticity disorder, as the main feature of pathophysiological changes in the brain after stroke, has become a cutting-edge hotspot in PSCI. Studies have shown that the transcription factor Maf1 is highly expressed in the central nervous system, it can regulate the formation of neuronal dendrites and dendritic spines, which is closely related to the occurrence of many neurological diseases. The purpose of this study is to explore the molecular regulatory which Maf1 affects the occurrence of PSCI. Methods This project employs PSCI mouse models (dMCAO models), MAF1flox/flox and Thy1-GFP transgenic hybrid mice, neural stem cells and neurons from healthy individuals both in vivo and in vitro. By applying comprehensive research methods from multiple disciplines such as cell and molecular biology, neuromorphology, optogenetics, behavior, and electrophysiology. Results The expression level of Maf1 was significantly upregulated in hippocampal neurons of the PSCI mouse model. The number of mature dendritic spines (mushroom-shaped) in the hippocampal neurons of mice with Maf1 knockdown increased significantly. Maf1 binds to a specific region of the Irgm1 gene promoter related to mitochondria, affecting its transcriptional level and thereby influencing mitochondrial function. Conclusions The expression level of the transcriptional regulatory factor Maf1 increases in PSCI. It regulates its expression by binding to the promoter region of the Irgm1 gene, thereby further regulating mitophagy and influencing synaptic function and learning and memory function. Conflict of interest Yingying Han, Hanzhi Wang and GangLi: nothing to disclose.