RESUMEN
RATIONALE AND OBJECTIVE: Environmental enrichment (EE) has been shown in old rats to improve learning and memory. Vitamin D (VitD) has also been shown to modulate age-related, cognitive dysfunction. As both EE and VitD could work to improve cognition via enhancement of neurotrophic factors, their effects might occlude one another. Therefore, a clinically relevant question is whether noted cognition-promoting effects of EE and VitD can co-occur. METHODS: Aged rats were housed for 6 weeks in one of three housing conditions: environmentally enriched (EE), socially enriched (SE), or standard condition (SC). Further, a 4th group was co-treated with VitD supplementation (400 IU kg-1 daily, 6 weeks) under EE conditions (EE + VitD). RESULTS: Treatment with VitD and EE housing were associated with higher score on measures of learning and memory and exhibited lower anxiety scores compared to EE alone, SE or SC as assayed in the elevated plus maze, Morris water maze, passive avoidance, and open field tasks. Additionally, in the EE + VitD group, mRNA expression levels of NGF, TrkA, BDNF, Nrf2, and IGF-1 were significantly higher compared to expression seen in the EE group. Furthermore, field potential recordings showed that EE + VitD resulted in a greater enhancement of hippocampal LTP and neuronal excitability when compared to EE alone. CONCLUSIONS: These findings demonstrate that in aged rats exposure to EE and VitD results in effects on hippocampal cognitive dysfunction and molecular mechanisms which are greater than effects of EE alone, suggesting potential for synergistic therapeutic effects for management of age-related cognitive decline.