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

The European Journal of Neuroscience
Carolina TecuatlEmilio J Galván

Abstract

The selective vulnerability of hippocampal area CA1 to ischemia-induced injury is a well-known phenomenon. However, the cellular mechanisms that confer resistance to area CA3 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 CA3. 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 CA3 to OGD-RP. The protective effect of TrkB activation was limited to area CA3, as OGD-RP caused permanent suppression of CA1 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 MK2206 in combination with BDNF lost the capability to resist the damage inflicted with OGD-RP. Consistently,...Continue Reading

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Citations

Jul 18, 2019·Clinical and Experimental Pharmacology & Physiology·Li MaBaoguo He
Sep 12, 2020·Critical Reviews in Food Science and Nutrition·Marco EmiliFiorenza Stagni
Jan 23, 2021·Neurobiology of Disease·Francesca TozziNicola Origlia
May 23, 2021·Neurochemistry International·Rajib PaulAnupom Borah
Sep 30, 2021·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Kathryn A Schiel

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