Resveratrol Mitigates Cognitive Impairments and Cholinergic Cell Loss in the Medial Septum in a Mouse Model of Gradual Cerebral Hypoperfusion.

Autor: Fagerli E; Peritz Scheinberg Cerebral Vascular Disease Research Laboratories, University of Miami Leonard M. Miller School of Medicine, Miami, FL 33136, USA.; Department of Neurology, University of Miami Leonard M. Miller School of Medicine, Miami, FL 33136, USA.; Neuroscience Program, University of Miami Leonard M. Miller School of Medicine, Miami, FL 33136, USA., Jackson CW; Peritz Scheinberg Cerebral Vascular Disease Research Laboratories, University of Miami Leonard M. Miller School of Medicine, Miami, FL 33136, USA.; Department of Neurology, University of Miami Leonard M. Miller School of Medicine, Miami, FL 33136, USA.; Neuroscience Program, University of Miami Leonard M. Miller School of Medicine, Miami, FL 33136, USA., Escobar I; Peritz Scheinberg Cerebral Vascular Disease Research Laboratories, University of Miami Leonard M. Miller School of Medicine, Miami, FL 33136, USA.; Department of Neurology, University of Miami Leonard M. Miller School of Medicine, Miami, FL 33136, USA.; Neuroscience Program, University of Miami Leonard M. Miller School of Medicine, Miami, FL 33136, USA., Ferrier FJ; Peritz Scheinberg Cerebral Vascular Disease Research Laboratories, University of Miami Leonard M. Miller School of Medicine, Miami, FL 33136, USA.; Department of Neurology, University of Miami Leonard M. Miller School of Medicine, Miami, FL 33136, USA.; Neuroscience Program, University of Miami Leonard M. Miller School of Medicine, Miami, FL 33136, USA., Perez Lao EJ; Peritz Scheinberg Cerebral Vascular Disease Research Laboratories, University of Miami Leonard M. Miller School of Medicine, Miami, FL 33136, USA.; Department of Neurology, University of Miami Leonard M. Miller School of Medicine, Miami, FL 33136, USA.; Neuroscience Program, University of Miami Leonard M. Miller School of Medicine, Miami, FL 33136, USA., Saul I; Peritz Scheinberg Cerebral Vascular Disease Research Laboratories, University of Miami Leonard M. Miller School of Medicine, Miami, FL 33136, USA.; Department of Neurology, University of Miami Leonard M. Miller School of Medicine, Miami, FL 33136, USA., Gomez J; Peritz Scheinberg Cerebral Vascular Disease Research Laboratories, University of Miami Leonard M. Miller School of Medicine, Miami, FL 33136, USA.; Department of Neurology, University of Miami Leonard M. Miller School of Medicine, Miami, FL 33136, USA., Dave KR; Peritz Scheinberg Cerebral Vascular Disease Research Laboratories, University of Miami Leonard M. Miller School of Medicine, Miami, FL 33136, USA.; Department of Neurology, University of Miami Leonard M. Miller School of Medicine, Miami, FL 33136, USA.; Neuroscience Program, University of Miami Leonard M. Miller School of Medicine, Miami, FL 33136, USA., Bracko O; Department of Neurology, University of Miami Leonard M. Miller School of Medicine, Miami, FL 33136, USA.; Neuroscience Program, University of Miami Leonard M. Miller School of Medicine, Miami, FL 33136, USA.; Department of Biology, University of Miami, Coral Gables, FL 33146, USA., Perez-Pinzon MA; Peritz Scheinberg Cerebral Vascular Disease Research Laboratories, University of Miami Leonard M. Miller School of Medicine, Miami, FL 33136, USA.; Department of Neurology, University of Miami Leonard M. Miller School of Medicine, Miami, FL 33136, USA.; Neuroscience Program, University of Miami Leonard M. Miller School of Medicine, Miami, FL 33136, USA.
Jazyk: angličtina
Zdroj: Antioxidants (Basel, Switzerland) [Antioxidants (Basel)] 2024 Aug 14; Vol. 13 (8). Date of Electronic Publication: 2024 Aug 14.
DOI: 10.3390/antiox13080984
Abstrakt: Vascular cognitive impairment and dementia (VCID) is the second leading cause of dementia. There is currently no effective treatment for VCID. Resveratrol (RSV) is considered an antioxidant; however, our group has observed pleiotropic effects in stroke paradigms, suggesting more effects may contribute to mechanistic changes beyond antioxidative properties. The main goal of this study was to investigate if administering RSV twice a week could alleviate cognitive declines following the induction of a VCID model. Additionally, our aim was to further describe whether this treatment regimen could decrease cell death in brain areas vulnerable to changes in cerebral blood flow, such as the hippocampus and medial septum. We hypothesized RSV treatments in a mouse model of gradual cerebral hypoperfusion protect against cognitive impairment. We utilized gradual bilateral common carotid artery stenosis (GBCCAS) via the surgical implantation of ameroid constrictor devices. RSV treatment was administered on the day of implantation and twice a week thereafter. Cerebral perfusion was measured by laser speckle contrast imaging, and cognitive functions, including the recognition memory, the spatial working memory, and associative learning, were assessed by novel object recognition (NOR), Y-maze testing, and contextual fear conditioning (CFC), respectively. RSV treatment did not alleviate cerebral perfusion deficits but mitigated cognitive deficits in CFC and NOR after GBCCAS. Despite these deficits, no hippocampal pathology was observed; however, cholinergic cell loss in the medial septum was significantly increased after GBCCAS. This cholinergic cell loss was mitigated by RSV. This study describes a novel mechanism by which chronic RSV treatments protect against a VCID-induced cognitive decline through the preservation of cholinergic cell viability to improve memory performance.
Databáze: MEDLINE
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