Abstract
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.
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MB has conceived and designed the concept and road map of the study, searched the literature collected the data, and drafted the manuscript. KAK, MH, ABH, AK, GB, and EH helped design the study, searched the literature, reviewed the manuscript, and helped with the revision of the manuscript. MS has critically reviewed the manuscript, designed the study, and helped in manuscript preparation. He is the archival author and attests to the integrity of the original data and the analysis reported in this manuscript. All authors have made substantive contribution and attest to approving the final manuscript.
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Bayat, M., Kohlmeier, K.A., Haghani, M. et al. Co-treatment of vitamin D supplementation with enriched environment improves synaptic plasticity and spatial learning and memory in aged rats. Psychopharmacology 238, 2297–2312 (2021). https://doi.org/10.1007/s00213-021-05853-4
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DOI: https://doi.org/10.1007/s00213-021-05853-4