Resveratrol Preconditioning Protects Against Ischemia-Induced Synaptic Dysfunction and Cofilin Hyperactivation in the Mouse Hippocampal Slice.

Autor: Escobar I; Peritz Scheinberg Cerebral Vascular Disease Research Laboratories, University of Miami Leonard M. Miller School of Medicine, PO Box 016960, Miami, FL, 33101, USA.; Department of Neurology, University of Miami Leonard M. Miller School of Medicine, PO Box 016960, Miami, FL, 33101, USA.; Neuroscience Program, University of Miami Leonard M. Miller School of Medicine, PO Box 016960, Miami, FL, 33101, USA., Xu J; Peritz Scheinberg Cerebral Vascular Disease Research Laboratories, University of Miami Leonard M. Miller School of Medicine, PO Box 016960, Miami, FL, 33101, USA.; Department of Neurology, University of Miami Leonard M. Miller School of Medicine, PO Box 016960, Miami, FL, 33101, USA.; Neuroscience Program, University of Miami Leonard M. Miller School of Medicine, PO Box 016960, Miami, FL, 33101, USA., Jackson CW; Peritz Scheinberg Cerebral Vascular Disease Research Laboratories, University of Miami Leonard M. Miller School of Medicine, PO Box 016960, Miami, FL, 33101, USA.; Department of Neurology, University of Miami Leonard M. Miller School of Medicine, PO Box 016960, Miami, FL, 33101, USA.; Neuroscience Program, University of Miami Leonard M. Miller School of Medicine, PO Box 016960, Miami, FL, 33101, USA., Stegelmann SD; Peritz Scheinberg Cerebral Vascular Disease Research Laboratories, University of Miami Leonard M. Miller School of Medicine, PO Box 016960, Miami, FL, 33101, USA.; Department of Neurology, University of Miami Leonard M. Miller School of Medicine, PO Box 016960, Miami, FL, 33101, USA., Fagerli EA; Peritz Scheinberg Cerebral Vascular Disease Research Laboratories, University of Miami Leonard M. Miller School of Medicine, PO Box 016960, Miami, FL, 33101, USA.; Department of Neurology, University of Miami Leonard M. Miller School of Medicine, PO Box 016960, Miami, FL, 33101, USA.; Neuroscience Program, University of Miami Leonard M. Miller School of Medicine, PO Box 016960, Miami, FL, 33101, USA., Dave KR; Peritz Scheinberg Cerebral Vascular Disease Research Laboratories, University of Miami Leonard M. Miller School of Medicine, PO Box 016960, Miami, FL, 33101, USA.; Department of Neurology, University of Miami Leonard M. Miller School of Medicine, PO Box 016960, Miami, FL, 33101, USA.; Neuroscience Program, University of Miami Leonard M. Miller School of Medicine, PO Box 016960, Miami, FL, 33101, USA., Perez-Pinzon MA; Peritz Scheinberg Cerebral Vascular Disease Research Laboratories, University of Miami Leonard M. Miller School of Medicine, PO Box 016960, Miami, FL, 33101, USA. perezpinzon@med.miami.edu.; Department of Neurology, University of Miami Leonard M. Miller School of Medicine, PO Box 016960, Miami, FL, 33101, USA. perezpinzon@med.miami.edu.; Neuroscience Program, University of Miami Leonard M. Miller School of Medicine, PO Box 016960, Miami, FL, 33101, USA. perezpinzon@med.miami.edu.
Jazyk: angličtina
Zdroj: Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics [Neurotherapeutics] 2023 Jul; Vol. 20 (4), pp. 1177-1197. Date of Electronic Publication: 2023 May 19.
DOI: 10.1007/s13311-023-01386-0
Abstrakt: Perturbations in synaptic function are major determinants of several neurological diseases and have been associated with cognitive impairments after cerebral ischemia (CI). Although the mechanisms underlying CI-induced synaptic dysfunction have not been well defined, evidence suggests that early hyperactivation of the actin-binding protein, cofilin, plays a role. Given that synaptic impairments manifest shortly after CI, prophylactic strategies may offer a better approach to prevent/mitigate synaptic damage following an ischemic event. Our laboratory has previously demonstrated that resveratrol preconditioning (RPC) promotes cerebral ischemic tolerance, with many groups highlighting beneficial effects of resveratrol treatment on synaptic and cognitive function in other neurological conditions. Herein, we hypothesized that RPC would mitigate hippocampal synaptic dysfunction and pathological cofilin hyperactivation in an ex vivo model of ischemia. Various electrophysiological parameters and synaptic-related protein expression changes were measured under normal and ischemic conditions utilizing acute hippocampal slices derived from adult male mice treated with resveratrol (10 mg/kg) or vehicle 48 h prior. Remarkably, RPC significantly increased the latency to anoxic depolarization, decreased cytosolic calcium accumulation, prevented aberrant increases in synaptic transmission, and rescued deficits in long-term potentiation following ischemia. Additionally, RPC upregulated the expression of the activity-regulated cytoskeleton associated protein, Arc, which was partially required for RPC-mediated attenuation of cofilin hyperactivation. Taken together, these findings support a role for RPC in mitigating CI-induced excitotoxicity, synaptic dysfunction, and pathological over-activation of cofilin. Our study provides further insight into mechanisms underlying RPC-mediated neuroprotection against CI and implicates RPC as a promising strategy to preserve synaptic function after ischemia.
(© 2023. The Author(s).)
Databáze: MEDLINE
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