PMID- 29577884 OWN - NLM STAT- MEDLINE DCOM- 20190401 LR - 20190401 IS - 1872-6240 (Electronic) IS - 0006-8993 (Linking) VI - 1688 DP - 2018 Jun 1 TI - Regional-specific effects of cerebral ischemia/reperfusion and dehydroepiandrosterone on synaptic NMDAR/PSD-95 complex in male Wistar rats. PG - 73-80 LID - S0006-8993(18)30158-6 [pii] LID - 10.1016/j.brainres.2018.03.023 [doi] AB - Excessive glutamate efflux and N-methyl-D-aspartate receptor (NMDAR) over-activation represent well-known hallmarks of cerebral ischemia/reperfusion (I/R) injury, still, expression of proteins involved in this aspect of I/R pathophysiology show inconsistent data. Neurosteroid dehydroepiandrosterone (DHEA) has been proposed as potent NMDAR modulator, but its influence on I/R-induced changes up to date remains questionable. Therefore, I/R-governed alteration of vesicular glutamate transporter 1 (vGluT1), synaptic NMDAR subunit composition, postsynaptic density protein 95 (PSD-95) and neuronal morphology alone or following DHEA treatment were examined. For that purpose, adult male Wistar rats were treated with a single dose of vehicle or DHEA (20 mg/kg i.p.) 4 h following sham operation or 15 min bilateral common carotid artery occlusion. Western blot was used for analyses of synaptic protein expressions in hippocampus and prefrontal cortex, while neuronal morphology was assessed using Nissl staining. Regional-specific postischemic changes were detected on protein level i.e. signs of neuronal damage in CA1 area was accompanied with hippocampal vGluT1, NR1, NR2B enhancement and PSD-95 decrement, while histological changes observed in layer III were associated with decreased NR1 subunit in prefrontal cortex. Under physiological conditions DHEA had no effect on protein and histological appearance, while in ischemic milieu it restored hippocampal PSD-95 and NR1 in prefrontal cortex to the control level. Along with intact neurons, ones characterized by morphology observed in I/R group were also present. Future studies involving NMDAR-related intracellular signaling and immunohistochemical analysis will reveal precise effects of I/R and DHEA treatment in selected brain regions. CI - Copyright (c) 2018 Elsevier B.V. All rights reserved. FAU - Zaric, Marina AU - Zaric M AD - Department of Molecular Biology and Endocrinology, Vinca Institute of Nuclear Sciences, University of Belgrade, Belgrade, Serbia. FAU - Drakulic, Dunja AU - Drakulic D AD - Department of Molecular Biology and Endocrinology, Vinca Institute of Nuclear Sciences, University of Belgrade, Belgrade, Serbia. FAU - Stojanovic, Ivana Gusevac AU - Stojanovic IG AD - Department of Molecular Biology and Endocrinology, Vinca Institute of Nuclear Sciences, University of Belgrade, Belgrade, Serbia. FAU - Mitrovic, Natasa AU - Mitrovic N AD - Department of Molecular Biology and Endocrinology, Vinca Institute of Nuclear Sciences, University of Belgrade, Belgrade, Serbia. FAU - Grkovic, Ivana AU - Grkovic I AD - Department of Molecular Biology and Endocrinology, Vinca Institute of Nuclear Sciences, University of Belgrade, Belgrade, Serbia. FAU - Martinovic, Jelena AU - Martinovic J AD - Department of Molecular Biology and Endocrinology, Vinca Institute of Nuclear Sciences, University of Belgrade, Belgrade, Serbia. Electronic address: jelenazlatkovic@vinca.rs. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180322 PL - Netherlands TA - Brain Res JT - Brain research JID - 0045503 RN - 0 (Disks Large Homolog 4 Protein) RN - 0 (Dlg4 protein, rat) RN - 0 (NR2B NMDA receptor) RN - 0 (Neuroprotective Agents) RN - 0 (Protein Subunits) RN - 0 (Receptors, N-Methyl-D-Aspartate) RN - 0 (Slc17a7 protein, rat) RN - 0 (Vesicular Glutamate Transport Protein 1) RN - 459AG36T1B (Dehydroepiandrosterone) SB - IM MH - Animals MH - Brain Ischemia/*metabolism/prevention & control MH - Dehydroepiandrosterone/*administration & dosage/metabolism MH - Disks Large Homolog 4 Protein/*metabolism MH - Hippocampus/drug effects/*metabolism MH - Male MH - Neuroprotective Agents/*administration & dosage MH - Prefrontal Cortex/drug effects/*metabolism MH - Protein Subunits/metabolism MH - Rats, Wistar MH - Receptors, N-Methyl-D-Aspartate/*metabolism MH - Reperfusion Injury/metabolism/prevention & control MH - Synapses/drug effects/*metabolism MH - Synaptosomes/metabolism MH - Vesicular Glutamate Transport Protein 1/metabolism OTO - NOTNLM OT - Cerebral ischemia/reperfusion OT - Dehydroepiandrosterone OT - Glutamatergic neurotransmission OT - Hippocampus OT - Prefrontal cortex OT - Synaptosomes EDAT- 2018/03/27 06:00 MHDA- 2019/04/02 06:00 CRDT- 2018/03/27 06:00 PHST- 2018/01/07 00:00 [received] PHST- 2018/03/16 00:00 [revised] PHST- 2018/03/17 00:00 [accepted] PHST- 2018/03/27 06:00 [pubmed] PHST- 2019/04/02 06:00 [medline] PHST- 2018/03/27 06:00 [entrez] AID - S0006-8993(18)30158-6 [pii] AID - 10.1016/j.brainres.2018.03.023 [doi] PST - ppublish SO - Brain Res. 2018 Jun 1;1688:73-80. doi: 10.1016/j.brainres.2018.03.023. Epub 2018 Mar 22.