Heterochronic bone marrow transplantation alters behavioral measures in middle-aged mice

Abstract Age-related declines in cognitive and motor function are influenced not only by intrinsic brain changes but also by systemic factors, including circulating blood components. Recent studies have suggested that rejuvenation of the hematopoietic system may influence brain ageing; however, the effects of bone marrow transplantation (BMT) during middle age remain poorly understood. In this study, we examined behavioral outcomes following heterochronic BMT in 8-month-old mice conditioned with busulfan and transplanted with bone marrow cells from either young (2-month-old) or age-matched donors. Three months post-transplantation, mice receiving young bone marrow showed changes in wire-hang performance and showed differences in open-field parameters, while recognition memory measured by the novel object recognition task was unchanged. Immunohistochemical analysis showed a tendency toward increased doublecortin- and EdU-positive cells in the dentate gyrus of young-donor BMT mice; however, this difference did not reach statistical significance. Together, these findings suggest that heterochronic BMT may be associated with changes in selected behavioral measures in middle-aged mice and warrant further studies to clarify the relationship between systemic factors and age-related brain changes.