TrkB‐mediated activation of the phosphatidylinositol‐3‐kinase/Akt cascade reduces the damage inflicted by oxygen–glucose deprivation in area CA3 of the rat hippocampus

• DOI: 10.1111/ejn.13880
• Publication Date: 2018-02-26T15:55:00Z
• Authors: Carolina Tecuatl; Gabriel Herrrera‐...; Alejandro Martín‐...; Bocheng Yin; Stephen Weber; Germán Barrionuevo; Emilio J. Galván
• Keywords: Male; Neurons; Cell Survival; Hippocampus; Oxygen; Rats, Sprague-Dawley; Phosphatidylinositol 3-Kinases; 03 medical and health sciences; Glucose; Neuroprotective Agents; 0302 clinical medicine; Animals; Receptor, trkB; Phosphorylation; Proto-Oncogene Proteins c-akt; Signal Transduction

Abstract The selective vulnerability of hippocampal area CA 1 to ischemia‐induced injury is a well‐known phenomenon. However, the cellular mechanisms that confer resistance 3 against ischemic damage remain elusive. Here, we show oxygen–glucose deprivation–reperfusion ( OGD ‐ RP ), an in vitro model mimic pathological conditions stroke, increases phosphorylation level tropomyosin receptor kinase B (TrkB) 3. Slices preincubated with brain‐derived neurotrophic factor BDNF ) or 7,8‐dihydroxyflavone (7,8‐ DHF exhibited reduced depression electrical activity triggered by . Consistently, blockade TrkB suppressed protective effect activation was limited 3, as caused permanent suppression responses. At level, leads accessory proteins SHC and Gab well serine/threonine Akt, members phosphoinositide 3‐kinase/Akt PI ‐3‐K/Akt) pathway, cascade involved cell survival. Hence, acute slices pretreated Akt antagonist MK 2206 combination lost capability resist inflicted these results, pyramidal cells propidium iodide uptake caspase‐3 exposed We propose ‐3‐K/Akt downstream mediated represents endogenous mechanism responsible for damage.