HIF-1? Is Critical For The Activation Of Notch Signaling In Neurogenesis During Acute Epilepsy

Objective To investigate the role of HIF-1? in neurogenesis and whether Notch signaling is involved in this process during epileptogenesis? Methods Pilocarpine epilepsy model was used.The SD rats were randomly divided into four groups,including control,epilepsy,epilepsy+2-methoxyestradiol(2ME2)and epilepsy+GSI-IX(DAPT)groups.1.The mRNA and protein expression levels of HIF-1? in acute epilepsy were examined by using western blot,PCR and immunohistochemistry.2.The role of HIF-1? and Notch signaling in the process of neurogenesis during epileptogenesis was estimated by assessing hippocampal neuronal injury,the proliferation and differentiation of neural stem cells(NSCs)with the metods of immunohistochemistry and immunofluorescence.3.The involvement of Notch signaling in HIF-1?-promoted neurogenesis was assessed by immunoprecipitation assay and immunofluorescence.Results 1.The expression of HIF-1? was found to be upregulated in a time-dependent pattern during acute epilepsy.2.HIF-1? upregulation mediated neurogenesis during epileptogenesis including hippocampal neuronal injury,the proliferation and differentiation of neural stem cells(NSCs),which required the participation of Notch signaling.3.The immunoprecipitation data illustrated that HIF-1? activated Notch signaling by physically interacting Notch intracellular domain(NICD)in epilepsy.Conclusions Our results suggested that HIF-1?-Notch signaling enhanced neurogenesis in acute epilepsy and that neurogenesis during epileptogenesis was reduced once this pathway was blocked;thus,members of this pathway might be potential therapeutic targets for epilepsy.