MicroRNAs (miRNAs/miRs) have been reported to affect ischemia/reperfusion (I/R)-induced cerebral damage. miRNAs cause post-transcriptional gene silencing by binding to the protein-coding sequence (CDS) of mRNAs. Seipin has a potential role in regulating autophagic flux. The present study investigated the involvement of miR-187-3p in Seipin expression, autophagic flux and apoptosis in vitro , as well as the underlying mechanism, using PC12 cells exposed to oxygen-glucose deprivation/reoxygenation (OGD/R), which mimicked the process of I/R. In comparison with control PC12 cells, OGD/R caused an increase in the level of miR-187-3p and a decrease in Seipin protein levels without changes in the level of Seipin mRNA. Using bioinformatics analysis, it was identified that miR-187-3p could bind to the CDS of Seipin. miR-187-3p inhibitor attenuated the reduction in Seipin protein expression in OGD/R-treated PC12 cells. Following OGD/R, autophagic flux was reduced and apoptosis was enhanced, which were attenuated by inhibition of miR-187-3p. Compared with OGD/R-treated PC12 cells, Seipin knockdown further impaired autophagic flux and promoted neuronal apoptosis, which were insensitive to inhibition of miR-187-3p. Furthermore, treatment with miR-187-3p inhibitor could decrease the infarction volume in a rat model of middle cerebral artery occlusion/reperfusion. The present findings indicated that miR-187-3p inhibitor attenuated ischemia-induced cerebral damage by rescuing Seipin expression to improve autophagic flux.

alzheimer's disease (ad) is a chronic and irreversible neurodegenerative disorder. abnormal aggregation of the neurotoxic amyloid-β (aβ) peptide is an early event in ad. The activation of astrocytic α7 nicotinic acetylcholine receptor (α7 nachr) can inhibit aβ aggregation; thus, the molecular mechanism between α7 nachr activation and aβ aggregation warrants further investigation. in the present study, aβ oligomer levels were assessed in astrocytic cell lysates after treatment with Pnu282987 (a potent agonist of α7 nachrs) or co-treatment with lY294002, a p-akt inhibitor. The levels of heat shock factor-1 (HSF-1), heat shock protein 70 (HSP-70), and αB-crystallin (cryab) in astrocytes treated with Pnu282987 at various time-points or co-treated with methyllycaconitine (Mla), a selective α7 nachr antagonist, as well as co-incubated with lY294002 were determined by western blotting. HSP-70 and cryab levels were determined after HSF-1 knockdown (Kd) in astrocytes. Pnu282987 markedly inhibited aβ aggregation and upregulated HSF-1, cryab, and HSP-70 in primary astrocytes, while the Pnu282987-mediated neuroprotective effect was reversed by pre-treatment with Mla or lY294002. Moreover, the HSF-1 Kd in astrocytes effectively decreased cryab, but not HSP-70 expression. HSF-1 is necessary for the upregulation of cryab expression, but not for that of HSP-70. HSF-1 and HSP-70 have a neuroprotective effect. Furthermore, the neuroprotective effect of Pnu282987 against aβ aggregation was mediated by the canonical Pi3K/akt signaling pathway activation.

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