Resveratrol mitigates activated astrocytes and microglia preventing Alzheimer's Disease (AD) progression and facilitates neuronal communication in Amyloid-β25-35 induced rat model for AD: A special emphasis on non-neuronal involvement in AD pathophysiology.
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引用次数: 0
Abstract
Rationale: Amyloid deposits initiate neuroinflammation by activating astrocytes and microglia in the hippocampus, increasing neuronal vulnerability and loss. Astrocytes, while essential for cerebral function, can contribute to neuronal dysfunction by retracting neuronal synapses, that forms a consequence of neuroinflammation, leading to cognitive deficits in Alzheimer's disease (AD). Upon Amyloid-β (Aβ) deposition, astrocytes become reactive as part of a repair mechanism, however this process can impair neurogenesis resulting in AD progression.
Objective: The current study hypothesizes that resveratrol (RSV) can address inflammation and promote neural regeneration, mitigating cognitive decline. Our previous research highlights RSV's homeostatic effect through SIRT1 normalization, which is crucial in preventing AD progression. However, its neurogenic potential in AD remains underexplored.
Methods: In this study, Aβ25-35-induced AD rat model was used to study the anti-inflammatory, neurogenic and cellular homeostatic effect of RSV (30 mg/kg) for four weeks.
Results: Results showed increased Doublecortin expressing cells, indicating favorable neurogenesis in hippocampus. Immunofluorescence of microglia and astrocytes in the hippocampus revealed that RSV counteracted their activation by reducing the formation of engulfing microglia and elongated astrocytes. Behavioral assessments using the Morris water maze and cued radial arm maze demonstrated significant improvements in spatial and learning memory. These cognitive improvements were supported by increased choline acetyltransferase and SIRT1 levels.
Conclusion: These findings suggest that RSV effectively reduces neuroinflammation, promotes neurogenesis in the sub granular zone of the hippocampus, and improves learning and memory in both control and AD conditions via SIRT1. This study highlights RSV's potential as a suitable therapeutic agent for AD.
期刊介绍：
Official Journal of the European Behavioural Pharmacology Society (EBPS)
Psychopharmacology is an international journal that covers the broad topic of elucidating mechanisms by which drugs affect behavior. The scope of the journal encompasses the following fields:
Human Psychopharmacology: Experimental
This section includes manuscripts describing the effects of drugs on mood, behavior, cognition and physiology in humans. The journal encourages submissions that involve brain imaging, genetics, neuroendocrinology, and developmental topics. Usually manuscripts in this section describe studies conducted under controlled conditions, but occasionally descriptive or observational studies are also considered.
Human Psychopharmacology: Clinical and Translational
This section comprises studies addressing the broad intersection of drugs and psychiatric illness. This includes not only clinical trials and studies of drug usage and metabolism, drug surveillance, and pharmacoepidemiology, but also work utilizing the entire range of clinically relevant methodologies, including neuroimaging, pharmacogenetics, cognitive science, biomarkers, and others. Work directed toward the translation of preclinical to clinical knowledge is especially encouraged. The key feature of submissions to this section is that they involve a focus on clinical aspects.
Preclinical psychopharmacology: Behavioral and Neural
This section considers reports on the effects of compounds with defined chemical structures on any aspect of behavior, in particular when correlated with neurochemical effects, in species other than humans. Manuscripts containing neuroscientific techniques in combination with behavior are welcome. We encourage reports of studies that provide insight into the mechanisms of drug action, at the behavioral and molecular levels.
Preclinical Psychopharmacology: Translational
This section considers manuscripts that enhance the confidence in a central mechanism that could be of therapeutic value for psychiatric or neurological patients, using disease-relevant preclinical models and tests, or that report on preclinical manipulations and challenges that have the potential to be translated to the clinic. Studies aiming at the refinement of preclinical models based upon clinical findings (back-translation) will also be considered. The journal particularly encourages submissions that integrate measures of target tissue exposure, activity on the molecular target and/or modulation of the targeted biochemical pathways.
Preclinical Psychopharmacology: Molecular, Genetic and Epigenetic
This section focuses on the molecular and cellular actions of neuropharmacological agents / drugs, and the identification / validation of drug targets affecting the CNS in health and disease. We particularly encourage studies that provide insight into the mechanisms of drug action at the molecular level. Manuscripts containing evidence for genetic or epigenetic effects on neurochemistry or behavior are welcome.
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