Enriched physical environment attenuates spatial and social memory impairments of aged socially isolated mice

Background: Social isolation in the elderly is one of the principal health risks in an aging society. Physical environmental enrichment is shown to improve sensory, cognitive, and motor functions, but it is unknown whether environmental enrichment can protect against brain impairments caused by social isolation. Methods: Eighteen-month-old mice were housed, either grouped or isolated, in a standard or enriched environment for 2 months, respectively. Behavioral tests were performed to evaluate cognitive functional and social interaction ability. Synaptic protein levels, myelination, neuroinflammation, brain derived neurotrophic factor, and NOD-like receptor protein 3 inflammasome signaling pathways were examined in the medial prefrontal cortex and hippocampus. Results: Isolated aged mice exhibited declines in spatial memory and social memory compared with age-matched littermates living within group housing. The aforementioned memory malfunctions were mitigated in isolated aged mice that were housed in a large cage with a running wheel and novel toys. Enriched housing prevented synaptic protein loss, myelination defects, and downregulation of brain derived neurotrophic factor, while also increasing interleukin 1 beta and tumor necrosis factor alpha in the medial prefrontal cortex and hippocampus of isolated mice. In addition, activation of glial cells and NOD-like receptor protein 3 inflammasomes was partially ameliorated in the hippocampus of isolated mice treated with physical environmental enrichment. Conclusions: These results suggest that an enriched physical environment program may serve as a nonpharmacological intervention candidate to help maintain healthy brain function of elderly people living alone.