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

Brain Research Bulletin
De-Yuan LiLi-Na Qiao

Abstract

AMP-activated protein kinase (AMPK) is a key metabolic and stress sensor/effector. Few investigations have been performed to study the role of AMPK in developing rat brain with hypoxia-ischemia (HI). Forkhead transcriptional factor (FOXO3a) has been revealed to be a critical effector of AMPK-mediated celluar apoptosis. However, it is not clear whether AMPK/FOXO3a pathway is involved in neuronal apoptosis in the developing rat brain after HI. 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 r...Continue Reading

Citations

Jun 24, 2019·The FEBS Journal·Emilie HollvilleMohanish Deshmukh
Feb 2, 2019·International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience·Mariko SaitoBhaskar C Das
May 17, 2019·Neural Plasticity·Mariangela GennaroTommaso Pizzorusso
Nov 7, 2021·Cellular and Molecular Life Sciences : CMLS·Rohan Gupta Pravir Kumar

❮ Previous
Next ❯

Related Concepts

Related Feeds

Brain Ischemia

Brain ischemia is a condition in which there is insufficient blood flow to the brain to meet metabolic demand. Discover the latest research on brain ischemia here.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

Auditory Perception

Auditory perception is the ability to receive and interpret information attained by the ears. Here is the latest research on factors and underlying mechanisms that influence auditory perception.