Effect of enriched environment on spatial memory and expression of microglial activation markers in Balb/c mice

Enriched habitat of laboratory animals causes stimulation of neuronal plasticity including increased level of hippocampal neurogenesis and more efficient spatial orientation. In addition, the enriched environment has an immunomodulatory effect on both peripheral immune cells and microglia, i.e., resident brain macrophages. Since immune cells and their secreted products modulate the processes of neuronal plasticity, studying the effects of enriched environment is relevant on the level of neurogenesis in rodents with different immune status. Compared with C57Bl/6, Balb/c mice are characterized by predominance of humoral (Th2) rather than cellular (Th1) types of immunity which is associated with differences in the H2 region of the major histocompatibility (MHCI) gene locus, as well as a higher level of anxiety revealed by behavioral phenotyping. The aim of our study was to evaluate the effect of enriched environment on spatial memory, levels of neurogenesis, and activation features of resident macrophages (microglia) in hippocampus of Balb/c mice. The study was performed on 4-month-old female Balb/c mice. To assess the spatial memory and learning ability, the Barnes labyrinth was used. Gene expression levels were assessed by means of gene-specific PCR using primers for BDNF, CD68, DCX, FGF2, IBA1, IL-1B, IL-10, SOX2, TMEM119, TNFα; GAPDH was used as a reference gene. The obtained data suggest that keeping Balb/c mice under the enriched conditions promotes increased levels of hippocampal neurogenesis, along with more efficient spatial orientation. Expression of genes encoding neurotrophic factors, as well as cytokines and markers of microglia activation proved to be increased for FGF2, TNFα, Iba1 and TMEM119, whereas expression of BDNF, IL-1β, IL-10 and CD68 genes did not change. Hence, expression of BDNF and IL-10 genes in Balb/c mice from enriched environment was not increased, being typical for C57BL/6 mice. However, it does not prevent the proliferation and differentiation of neurons in gyrus dentatus and successful spatial orientation in Barnes labyrinth. Microglial cells in Balb/c mice under enriched conditions are probably polarized according to the M0/M2 type.