title: PTEN inhibition prevents rat cortical neuron injury after hypoxia-ischemia.
abstract: Alterations in axon-dendrite polarity impair functional recovery in the developing CNS after hypoxia-ischemia (HI) injury. PTEN (phosphatase and tensin homolog deleted on chromosome 10) signaling pathway mediates the formation of neuronal polarity. However, its role in cerebral HI injury is not fully understood. In this study, we investigated the role of PTEN pathway in regulation of axon-dendrite polarity using an oxygen-glucose deprivation (OGD) model with rat cortical neurons. We found that the activity of PTEN and glycogen synthase kinase 3β (GSK-3β) was increased after OGD, along with the decrease of the activity in protein kinase B (Akt) and collapsin response mediator protein-2 (CRMP-2). Pretreatment with bpv, a potent inhibitor of PTEN, caused a decrease of the activity in PTEN and GSK-3β, and a significant increase of the activity in Akt and CRMP-2. Simultaneously, the morphological polarity of neurons was maintained and neuronal apoptosis was reduced. Moreover, inhibition of PTEN rescued vesicle recycling in axons. These findings suggested that the PTEN/Akt/GSK-3β/CRMP-2 pathway is involved in the regulation of axon-dendrite polarity, providing a novel route for protecting neurons following neonatal HI.
authors: Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu 610041, China.
authors: J
authors: J
authors: Zhao
authors: Y
authors: Y
authors: Qu
authors: J
authors: J
authors: Wu
authors: M
authors: M
authors: Cao
authors: D M
authors: DM
authors: Ferriero
authors: L
authors: L
authors: Zhang
authors: D
authors: D
authors: Mu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D020925:Hypoxia-Ischemia, Brain / Q000378:metabolism* / Q000473:pathology; D036341:Intercellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051059:PTEN Phosphohydrolase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; C095114:collapsin response mediator protein-2; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3; D051059:PTEN Phosphohydrolase; C487216:Pten protein, rat