PMID- 29480936 OWN - NLM STAT- MEDLINE DCOM- 20191119 LR - 20230817 IS - 1460-9568 (Electronic) IS - 0953-816X (Print) IS - 0953-816X (Linking) VI - 47 IP - 9 DP - 2018 May TI - 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. PG - 1096-1109 LID - 10.1111/ejn.13880 [doi] AB - 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, with these results, CA3 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 CA3 to ischemic damage. CI - (c) 2018 Federation of European Neuroscience Societies and John Wiley & Sons Ltd. FAU - Tecuatl, Carolina AU - Tecuatl C AD - Departamento de Farmacobiologia, Centro de Investigacion y de Estudios Avanzados del Instituto Politecnico Nacional, Calzada de los Tenorios No. 235, Mexico City, 14330, Mexico. FAU - Herrrera-Lopez, Gabriel AU - Herrrera-Lopez G AD - Departamento de Farmacobiologia, Centro de Investigacion y de Estudios Avanzados del Instituto Politecnico Nacional, Calzada de los Tenorios No. 235, Mexico City, 14330, Mexico. FAU - Martin-Avila, Alejandro AU - Martin-Avila A AD - Departamento de Farmacobiologia, Centro de Investigacion y de Estudios Avanzados del Instituto Politecnico Nacional, Calzada de los Tenorios No. 235, Mexico City, 14330, Mexico. FAU - Yin, Bocheng AU - Yin B AD - Department of Chemistry, University of Pittsburgh, Pittsburgh, PA, USA. FAU - Weber, Stephen AU - Weber S AD - Department of Chemistry, University of Pittsburgh, Pittsburgh, PA, USA. FAU - Barrionuevo, German AU - Barrionuevo G AD - Department of Neuroscience, University of Pittsburgh, Pittsburgh, PA, USA. FAU - Galvan, Emilio J AU - Galvan EJ AUID- ORCID: 0000-0002-9820-302X AD - Departamento de Farmacobiologia, Centro de Investigacion y de Estudios Avanzados del Instituto Politecnico Nacional, Calzada de los Tenorios No. 235, Mexico City, 14330, Mexico. LA - eng GR - R01 NS037459/NS/NINDS NIH HHS/United States GR - R01 GM066018/GM/NIGMS NIH HHS/United States GR - R01 GM044842/GM/NIGMS NIH HHS/United States GR - RF1 NS037459/NS/NINDS NIH HHS/United States GR - R56 NS037459/NS/NINDS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20180325 PL - France TA - Eur J Neurosci JT - The European journal of neuroscience JID - 8918110 RN - 0 (Neuroprotective Agents) RN - EC 2.7.1.- (Phosphatidylinositol 3-Kinases) RN - EC 2.7.10.1 (Receptor, trkB) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - IY9XDZ35W2 (Glucose) RN - S88TT14065 (Oxygen) SB - IM MH - Animals MH - Cell Survival/drug effects MH - Glucose/*metabolism MH - Hippocampus/drug effects/*metabolism MH - Male MH - Neurons/drug effects/metabolism MH - Neuroprotective Agents/pharmacology MH - Oxygen/*metabolism MH - Phosphatidylinositol 3-Kinases/drug effects/*metabolism MH - Phosphorylation MH - Proto-Oncogene Proteins c-akt/metabolism MH - Rats, Sprague-Dawley MH - Receptor, trkB/*metabolism MH - Signal Transduction/drug effects PMC - PMC5938095 MID - NIHMS946052 OTO - NOTNLM OT - CA3 pyramidal cells OT - PI-3-K/Akt OT - Reperfusion OT - brain-derived neurotrophic factor OT - mossy fibers OT - tropomyosin receptor kinase B EDAT- 2018/02/27 06:00 MHDA- 2019/11/20 06:00 PMCR- 2019/05/01 CRDT- 2018/02/27 06:00 PHST- 2017/09/08 00:00 [received] PHST- 2018/02/17 00:00 [revised] PHST- 2018/02/20 00:00 [accepted] PHST- 2018/02/27 06:00 [pubmed] PHST- 2019/11/20 06:00 [medline] PHST- 2018/02/27 06:00 [entrez] PHST- 2019/05/01 00:00 [pmc-release] AID - 10.1111/ejn.13880 [doi] PST - ppublish SO - Eur J Neurosci. 2018 May;47(9):1096-1109. doi: 10.1111/ejn.13880. Epub 2018 Mar 25.