Abstract Sun206: Adipocyte-derived small extracellular vesicles and miR-29c-3p promoted apoptosis of cortical neurons in obese mice after resuscitation via downregulating neuronal MCL1

Abstract

Background: Compared with normal weight patients, obese patients had a lower survival rate and worse neurological prognosis after cardiopulmonary resuscitation (CPR). Cortical neuron apoptosis contributes to brain damage following CPR, and the endocrine dysfunction of adipocytes is closely linked to neuronal damage. As an important mediator of intercellular communication, the number and function of plasma small extracellular vesicles (Pla-sEV) and adipocyte-derived extracellular vesicles (Adipo-sEV) in obese people are significantly changed. However, whether and how Adipo-sEV exacerbates the apoptosis of cortical neurons after CPR remains unclear. Methods: The Obese mice cardiac arrest (CA) model was established by inducing ventricular fibrillation electrically. The sEVs were injected through the tail vein of mice to evaluate the apoptotic effects of Adipo-sEV derived from obesity mice (Adipo-sEV ob/ob ) on cortical neurons. Neuronal apoptosis was evaluated by TUNEL staining and the expression of cleaved caspase 3. Bioinformatics analysis was conducted to screen for pro-apoptotic miRNAs in sEVs and confirmed the expression by RT-qPCR. Results: Compared with the lean group, obese mice exhibited a significant increase in cortical neuron apoptosis after return of spontaneous circulation (ROSC). Pla-sEV and Adipo-sEV from obese mice can be taken up by cortical neurons and promote apoptosis in cortical neurons after ROSC. We screened miR-29c-3p from the database, which is adipose-specific and can promote neuron apoptosis. We further identified that antagonising miR-29c-3p in Adipo-sEV alleviated cortical neuron apoptosis in obese mice after ROSC. miR-29c-3p downregulated Mcl1 expression via directly binding to the 3' UTR region of Mcl1 mRNA. Conclusion: These results suggest that the Adipo-sEV ob/ob and miR-29c-3p promoted cortical neurons apoptosis in mice after ROSC via downregulating the expression of Mcl1 .