Environmental enrichment enhances neurogenesis and improves functional outcome after cranial irradiation

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Abstract
Radiation therapy is a widely used treatment for brain tumors but it can cause delayed progressive cognitive decline and memory deficits. Previous studies suggested that this neurocognitive dysfunction might be linked to the impairment of hippocampal neurogenesis. However, little is known regarding how to reduce the cognitive impairment caused by radiation therapy. To investigate whether environmental enrichment (EE) promotes neurogenesis and cognitive function after irradiation, irradiated gerbils were housed in EE for 2 months and evaluated by neurobehavioral testing for learning and memory function, and immunohistochemical analysis for neurogenesis. Our results demonstrated that even relatively low doses (5–10 Gy) of irradiation could acutely abolish precursor cell proliferation in the dentate gyrus by more than 90%. This reduction in precursor proliferation was persistent and led to a significant decline in the granule cell population 9 months later. EE housing enhanced the number of newborn neurons and increased residual neurogenesis. EE also significantly increased the total number of immature neurons in the dentate gyrus. Furthermore, irradiated animals after EE housing showed a significant improvement in spatial learning and memory during the water-maze test and in rotorod motor learning over a 5-day training paradigm. In conclusion, EE has a positive impact on hippocampal neurogenesis and functional recovery in irradiated adult gerbils. Our data suggest that there is still a considerable amount of plasticity remaining in the hippocampal progenitor cells in adult animals after radiation injury, which can become a target of therapeutic intervention for radiation-induced cognitive dysfunction.