Erythropoietin and sonic hedgehog mediate the neuroprotective effects of brain-derived neurotrophic factor against mitochondrial inhibition

摘要: Abstract Brain-derived neurotrophic factor (BDNF) deficiency and mitochondrial dysfunction have been implicated in the pathogenesis of Huntington's disease (HD). 3-Nitropropionic acid (3-NP) is a inhibitor commonly used as pharmacological model mimicking HD. We recently reported that preconditioning primary rat cortical cultures with BDNF induces sonic hedgehog (SHH), which contributes to protective effects against 3-NP neurotoxicity. Because carbamylated erythropoietin (EPO) may induce SHH, we investigated whether BDNF-dependent SHH expression resistance require prior induction EPO. found induced EPO at both mRNA protein levels. BDNF-mediated were abolished by soluble receptor (sEPO-R), an inhibitor. Recombinant (rEPO) attenuated The rEPO-dependent neuroprotection was suppressed cyclopamine (CPM); however, sEPO-R failed affect neuroprotection. Furthermore, not neutralizing antibody, completely same dosage. Overall, our results demonstrate EPO, thus establishing signaling cascade “BDNF → EPO → SHH → 3-NP resistance” neurons.