Enriched environment improves memory function by promoting synaptic remodeling in vascular dementia rats☆

Vascular dementia (VaD), attributed to cerebrovascular pathology, is a leading cause of cognitive decline, characterized by memory loss, bradyphrenia, and affective lability, with memory deficits being particularly pronounced. The potential of enriched environment (EE) to ameliorate cognitive impairments by enhancing hippocampal synaptic plasticity, neurogenesis, and white matter remodeling has garnered considerable interest. In this study, we used a rat model for VaD through the procedure of bilateral common carotid artery ligation (BCCAO). We randomly assigned male Sprague-Dawley (SD) rats to three groups: the control sham-operated group (Sham group), the surgery-induced dementia group (BCCAO group), and the surgery-induced dementia group with enriched environment (EE group). The Sham and BCCAO groups were kept under standard lab conditions, whereas the EE group was housed in an enriched setting. Employing a behavioral assay battery, we observed that EE intervention significantly improved the spatial learning and memory performance in the Morris water maze. Subsequent neuromorphological assessments utilizing transmission electron microscopy disclosed an increase in synaptic density and postsynaptic density (PSD) thickness within the hippocampal CA1 region, indicative of structural synaptic modulation. Further probing into the molecular underpinnings revealed that EE upregulated the expression of PSD95, corroborating its role in enhancing cognitive faculties. Additionally, our investigation into the PGC-1 alpha/FNDC5/BDNF pathway demonstrated that EE intervention elevated the expression of these neurotrophic factors, suggesting a mechanistic link to synaptic and cognitive restoration. In summation, our findings elucidate the neurorestorative potential of EE in a preclinical VaD model, presenting a nonpharmacological intervention that modulates synaptic architecture and activates neuroprotective pathways. The observed correlations between synaptic remodeling and cognitive enhancement underscore the therapeutic relevance of EE in VaD, warranting further investigation for clinical applications.