Frontline Evidence on Resveratrol Co-treatment Mitigates Olfactory Granule Cell Layer Degeneration and Restores Subventricular Neurogenesis in an Aβ25–35 Rat Model of Alzheimer’s Disease

Amyloid aggregation during Alzheimer's disease (AD) not only damages memory-associated brain regions but also disrupts olfactory structures prior to clinical manifestation. Olfactory dysfunction is an early hallmark of AD and is closely associated with impaired subventricular zone (SVZ) neurogenesis in vivo. However, the mechanistic link between hippocampal amyloid toxicity and SVZ–olfactory bulb (OB) alterations remains insufficiently understood. In this study, intrahippocampal (CA1) administration of Aβ25–35 in rats induced pronounced astrocytic activation within the SVZ stem cell niche, leading to significant depletion of vimentin-positive neural stem/progenitor cells (NSPCs). This was accompanied by a marked reduction in doublecortin (DCX) expression, indicating impaired neurogenesis. Histological assessment further revealed disorganization and neuronal loss in the OB granular cell layer (GCL), reflecting compromised olfactory circuitry during AD progression. Resveratrol (RSV) 30 mg/kg was administered for four consecutive weeks following amyloid induction. To evaluate prolonged therapeutic efficacy beyond active drug exposure, animals were euthanized two weeks after the final RSV dose. This design enabled assessment of sustained neuropathological effects of Aβ25–35 and prolonged neuroprotective outcomes of RSV. RSV significantly attenuated astrocytic hyperactivation, preserved vimentin-positive NSPCs, restored DCX expression, and improved OB-GCL cytoarchitecture, indicating persistent neurogenic and structural recovery. Collectively, these findings demonstrate that hippocampal amyloid toxicity disrupts SVZ neurogenesis via astrocyte-mediated stem cell depletion, while RSV exerts sustained neuroprotective and disease-modifying effects that extend beyond the treatment period.