Involvement of the Akt/GSK-3β/CRMP-2 pathway in axonal injury after hypoxic-ischemic brain damage in neonatal rat

Neuroscience
T XiongD Mu

Abstract

Akt has been demonstrated as a survival kinase in brain after hypoxia-ischemia (HI). Previous studies have shown that glycogen synthase kinase-3β (GSK-3β)/collapsin response mediator protein 2 (CRMP-2) signaling pathway could be regulated by Akt for axonal-dendritic polarity. CRMP-2 is associated also with microtubule-mediated trafficking. However, whether Akt could regulate GSK-3β/CRMP-2 pathway and the possible effects of this regulation is unclear in developing brain after HI. In this study, we detected the expression of total and phosphorylated Akt, GSK-3β, and CRMP-2, as well as the axonal injury marker amyloid precursor protein (APP) by utilizing an HI model in postnatal 10-day rats. Axonal loss was determined by Bielschowsky silver impregnation, and histological injury was evaluated by hematoxylin and eosin (H&E) staining. We found that the phosphorylation of Akt was accompanied by phosphorylation of GSK-3β and dephosphorylation of CRMP-2 after HI. Furthermore, Akt inhibition significantly decreased the phosphorylation of GSK-3β and dephosphorylation of CRMP-2. Moreover, the down-regulation of dephosphorylated CRMP-2 was associated with increased axonal injury (increased APP expression and axonal loss). Our findings sugg...Continue Reading

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Citations

Jul 19, 2013·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Linnea StridhCarina Mallard
Mar 9, 2013·Journal of Neurochemistry·Minghui TanMingtao Li
Mar 13, 2015·Molecular Brain·Wenliang ChenHong-Shuo Sun
Jul 20, 2018·Developmental Neurobiology·Marie-Pier GirouardAlyson E Fournier
Mar 6, 2018·Journal of Neuropathology and Experimental Neurology·Tao XiongDezhi Mu
Mar 4, 2017·CNS Neuroscience & Therapeutics·Sammen HuangZhong-Ping Feng
Sep 5, 2014·Experimental and Therapeutic Medicine·Xiaojuan LiXiaoyin Wang
Mar 26, 2021·Frontiers in Aging Neuroscience·Biyao WangXinwen Zhang
May 18, 2021·BioMed Research International·Jinhua TangJun Yang
May 11, 2021·CNS & Neurological Disorders Drug Targets·Mohammad ZamanianGholamreza Bazmandegan

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