AMPK activates FOXO3a and promotes neuronal apoptosis in the developing rat brain during the early phase after hypoxia-ischemia.

In this study, we generated hypoxia-ischemia brain damage (HIBD) model using postnatal day 7 rats. We found that activation of AMPK was accompanied by the decrease of p-mTOR, p-Akt and p-FOXO3a, which induced FOXO3a translocation into the nucleus and up-regulated the expression of Bim and cleaved caspase 3 (CC3). Furthermore, we discovered that AMPK inhibition by Compound C, a selective inhibitor for AMPK activity, significantly increased the phosphorylation levels of mTOR, Akt and FOXO3a, attenuated the nuclear translocation of FOXO3a, and inhibited Bim and CC3 expression after HI. Moreover, AMPK inhibition reduced cellular apoptosis, attenuated brain infarct volume and promoted neurological recovery in the developing rat brain after HI. Our findings suggest that AMPK participates in the regulation of FOXO3a-mediated neuronal apoptosis in the developing rat brain after HI. Agents targeting AMPK may offer promise for rescuing neurons from HI-induced damage. PMID: 28499802 [PubMed - as supplied by publisher]
Source: Brain Research Bulletin - Category: Neurology Authors: Tags: Brain Res Bull Source Type: research