6. Enhanced recruitment of bone marrow-derived cells into the brain parenchyma in senescence-accelerated mice

Perturbation in the brain–immune interaction may play a role in the pathogenesis of neurodegenerative diseases. The senescence-accelerated mouse prone 10 (SAMP10) mice undergo early onset of age-related neurodegenerative changes and impaired cognition. Given the elevated levels of brain pro-inflammatory cytokines, dystrophic microglia and defects in cytokine-mediated neuroprotective glial responses, as well as an early involution of the thymus and impaired T cell functions, the brain–immune interaction could be perturbed in SAMP10 mice. We created radiation chimeras in which bone marrow cells of young and old SAMP10 and C57BL/6 (B6) mice were reconstituted by bone marrow cells derived from GFP transgenic B6 mice by intra-bone marrow–bone marrow transplantation (IBM–BMT) and analyzed these chimeras 4 months after BMT. In chimeras in which B6 mice were recipients, donor-derived cells entered several discrete regions of the brain parenchyma mostly adjacent to the tenia of the choroid plexus but not the remaining major parts of the brain parenchyma. On the other hand, in chimeras in which old SAMP10 mice were recipients, a larger number of donor-derived cells entered more regions, such as hypothalamus, white matter and brain stem, than in chimeras with B6 mice being recipients. The enhanced recruitment of bone marrow-derived cells into the brain parenchyma in old SAMP10 mice may be a manifestation of disturbances in the brain–immune interaction that might be related to early onset neurodegenerative changes.