Abstract
Irisin, a 112-amino acid peptide induced with exercise in mice and human is thought to have correlation with the short-term outcomes of patients in ischemic stroke. In the present study, the neuroprotective effects of irisin were evaluated in vivo and in vitro and its underlying mechanism was also explored. The global cerebral ischemia/reperfusion (I/R) model was established by bilateral common carotid artery occlusion for 20 min and reperfusion for 24 h in mice and oxygen-glucose deprivation/reperfusion in HT22 cells. Neurological function was scored and then the mice were sacrificed. The brains were harvested for HE staining and detection of brain water content (BWC). The percentage of neuronal apoptosis was evaluated by TUNEL and flow cytometry analysis. The mRNA expression of TNF-α and IL-1β was detected by RT-PCR analysis. The Notch intracellular domain (NICD) was detected by double immunofluorescence staining and western blot, and the protein expression of Notch1 and Hes 1 was detected by western blot. It was observed that irisin could alleviate morphological damage and improve neurological function after global cerebral I/R injury in mice. The apoptosis of hippocampal neurons reduced in the presence of irisin in vivo and in vitro. Additionally irisin could downregulate the expression of IL-1β and TNF-α and upregulate the expression of NICD, Notch1 and Hes 1 in vitro and in vivo. After the application of γ-secretase inhibitor DAPT, all the morphological, neurological and biochemical changes were reversed. Taken together, these results suggest that irisin could regulate the Notch signaling pathway that leads to the alleviation of transient global cerebral I/R injury.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.