Adipose stem cell-derived extracellular vesicles ameliorates corticosterone-induced apoptosis in the cortical neurons via inhibition of ER stress
2022
Sung-Ae Hyun | Young Ju Lee | Sumi Jang | Moon Yi Ko | Chang Youn Lee | Yong Woo Cho | Ye Eun Yun | Byoung-Seok Lee | Joung-Wook Seo | Kyoung-Sik Moon | Minhan Ka
Abstract Background Corticosterone (CORT) can induce neuronal damage in various brain regions, including the cerebral cortex, the region implicated in depression. However, the underlying mechanisms of these CORT-induced effects remain poorly understood. Recently, many studies have suggested that adipose stem cell-derived extracellular vesicles (A-EVs) protect neurons in the brain. Methods To investigated neuroprotection effects of A-EVs in the CORT-induced cortical neurons, we cultured cortical neurons from E15 mice for 7 days, and the cultured cortical neurons were pretreated with different numbers (5 × 105–107 per mL) of A-EVs (A-EVs5, A-EVs6, A-EVs7) for 30 min followed by administration of 200 μM CORT for 24 h. Results Here, we show that A-EVs exert antiapoptotic effects by inhibiting endoplasmic reticulum (ER) stress in CORT-induced cortical neurons. We found that A-EVs prevented neuronal cell death induced by CORT in cultured cortical neurons. More importantly, we found that CORT exposure in cortical neurons resulted in increased levels of apoptosis-related proteins such as cleaved caspase-3. However, pretreatment with A-EVs rescued the levels of caspase-3. Intriguingly, CORT-induced apoptosis involved upstream activation of ER stress proteins such as GRP78, CHOP and ATF4. However, pretreatment with A-EVs inhibited ER stress-related protein expression. Conclusion Our findings reveal that A-EVs exert antiapoptotic effects via inhibition of ER stress in CORT-induced cell death.
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