EFFECTS OF ENVIRONMENTAL ENRICHMENT ON HIPPOCAMPAL MICROGLIA AND THEIR RELATIONSHIP WITH ADULT NEUROGENESIS

An active lifestyle induces structural and functional brain changes that promote healthy aging. This phenomenon has been studied in the hippocampus, which exhibits high plasticity, including the production of new neurons in the dentate gyrus during adulthood (adult hippocampal neurogenesis: AHN). Previous studies have focused on the effects of environmental enrichment (EE) on the production of new neurons; however, the cellular mechanisms by which lifestyle modulates AHN remain unclear.
In this study, we investigated the effect of EE on microglia in the molecular layer (ML) of the dentate gyrus (DG), as microglia have the potential to detect changes in their microenvironment and consequently modulate AHN. We housed two-month-old mice in EE for six weeks and compared them with standard-housed controls. Our results indicate that EE increases DG size and immature neuron dendritic density in the ML. Additionally, EE reduces microglial area without changing their number in the ML. Furthermore, our colocalization analyses suggest that EE decreases microglial surveillance of new dendrites. To better understand this phenomenon, we are also analysing how EE influences the transcriptomic profile of DG tissue extracted from mice exposed to EE or standard housing for six weeks.
Our results demonstrate that EE is indeed affecting microglial morphology and their proximity to newly generated neurons. This suggests that microglia may act as modulatory mechanisms through which an active lifestyle induces changes in hippocampal plasticity.

Funding: MICINN PID2022-140525NB-I00 and PID2022-140456NB-I00. Erasmus+ programme Partnership for Cooperation (2023-1-PL01-KA220-HED-000160284). JCyL-FEDER co-funded by the ERDF Operational Programme (CLU-2023-1-01). MICINN FPU23/00987.