ASPROSIN AS A NEW REGULATOR OF MURINE HIPPOCAMPAL HT-22 CELLS FUNCTION

Asprosin is a recently identified protein hormone derived from profibrillin-1 that regulates energy metabolism, glycemia, and appetite. Increasing evidence suggests that asprosin crosses blood-brain barrier and acts on neurons of central nervous system. However, its role in hippocampal neurons remains unclear. This study aimed to determine presence of asprosin system components and investigate effect of exogenous asprosin on viability, proliferation, cell cycle, and apoptosis of mouse hippocampal HT-22 cells. The expression of Fbn1, Asprosin, Furin, and Olfr734 was evaluated at mRNA and protein levels using reverse transcription quantitative polymerase chain reaction (RT-qPCR), western blot, and immunocytochemistry. The effects of asprosin (1, 10,and 100 nM; 7 and 24h of incubation) on viability, proliferation, and cell cycle were analyzed using alamarBlue and bromodeoxyuridine assays and flow cytometry. Moreover, markers of cell cycle (cyclins D1, E1, A2, B1) and apoptotic (Caspases-3, -8, -9, Bax, Bcl2) were examined by RT-qPCR and western blot. Fbn1, Asprosin, Furin, and Olfr734 were expressed in HT-22 cells. Asprosin affected cell viability and proliferation in a dose-dependent manner: low concentrations (1 nM) had no significant effect, whereas 10 and 100 nM significantly reduced viability. Higher concentrations decreased cyclin D1 and cyclin E1 levels, increased caspase-3 and caspase-8 mRNA, and decreased their protein expression, suggesting oxidative stress, impaired translation, and activation of mitochondrial death pathways. These findings demonstrate, for the first time, the presence of an asprosin system in hippocampal neurons and indicate that asprosin modulates proliferation and apoptosis in a dose-dependent manner, linking systemic metabolism with hippocampal functions.
Funding:2021/42/E/NZ4/00088