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TrkB‐mediated activation of the phosphatidylinositol‐3‐kinase/Akt cascade reduces the damage inflicted by oxygen–glucose deprivation in area CA 3 of the rat hippocampus
Author(s) -
Tecuatl Carolina,
HerrreraLópez Gabriel,
MartínÁvila Alejandro,
Yin Bocheng,
Weber Stephen,
Barrionuevo Germán,
Galván Emilio J.
Publication year - 2018
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/ejn.13880
Subject(s) - protein kinase b , tropomyosin receptor kinase b , hippocampus , phosphatidylinositol , pi3k/akt/mtor pathway , neuroscience , kinase , chemistry , microbiology and biotechnology , phosphorylation , biology , signal transduction , biochemistry , receptor , neurotrophic factors
The selective vulnerability of hippocampal area CA 1 to ischemia‐induced injury is a well‐known phenomenon. However, the cellular mechanisms that confer resistance to area CA 3 against ischemic damage remain elusive. Here, we show that oxygen–glucose deprivation–reperfusion ( OGD ‐ RP ), an in vitro model that mimic the pathological conditions of the ischemic stroke, increases the phosphorylation level of tropomyosin receptor kinase B (TrkB) in area CA 3. Slices preincubated with brain‐derived neurotrophic factor ( BDNF ) or 7,8‐dihydroxyflavone (7,8‐ DHF ) exhibited reduced depression of the electrical activity triggered by OGD ‐ RP . Consistently, blockade of TrkB suppressed the resistance of area CA 3 to OGD ‐ RP . The protective effect of TrkB activation was limited to area CA 3, as OGD ‐ RP caused permanent suppression of CA 1 responses. At the cellular level, TrkB activation leads to phosphorylation of the accessory proteins SHC and Gab as well as the serine/threonine kinase Akt, members of the phosphoinositide 3‐kinase/Akt ( PI ‐3‐K/Akt) pathway, a cascade involved in cell survival. Hence, acute slices pretreated with the Akt antagonist MK 2206 in combination with BDNF lost the capability to resist the damage inflicted with OGD ‐ RP . Consistently, with these results, CA 3 pyramidal cells exhibited reduced propidium iodide uptake and caspase‐3 activity in slices pretreated with BDNF and exposed to OGD ‐ RP . We propose that PI ‐3‐K/Akt downstream activation mediated by TrkB represents an endogenous mechanism responsible for the resistance of area CA 3 to ischemic damage.