EFFECT OF ENRICHED ENVIRONMENT ON SPATIAL MEMORY AND EXPRESSION OF MICROGLIAL ACTIVATION MARKERS IN BALB/C MICE

Abstract

Enrichment of the habitat of laboratory animals stimulates neuronal plasticity processes, including increasing the level of hippocampal neurogenesis and more efficient spatial orientation. In addition, an enriched environment has an immunomodulatory effect on both peripheral immune cells and resident brain macrophages - microglia. Since immune cells and the molecules they secrete modulate the processes of neuronal plasticity, it is relevant to study the effect of an enriched environment on the level of neurogenesis in rodents with different immune status. Compared with C57Bl/6, Balb/c mice are characterized by a predominance of humoral (Th2) rather than cellular (Th1) types of immune response, which is associated with differences in the H2 region of the major histocompatibility gene locus MHCI, 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, the level of neurogenesis, and signs of activation of resident macrophages (microglia) in the 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 maze was used; to assess expression levels, a PCR was performed using gene-specific primers for BDNF, CD68, DCX, FGF2, IBA1, IL-1B, IL-10, SOX2, TMEM119, TNF-α; GAPDH was used as a reference gene. The obtained data suggest that keeping Balb/c mice in enriched conditions promotes an increase in the level of neurogenesis in the hippocampus and more efficient spatial orientation. Analysis of the expression of neurotrophic factors, as well as cytokines and markers of activation of resident brain macrophages (microglia) showed an increase in the expression of FGF2, TNF-α, Iba1 and TMEM119, while the expression levels of BDNF, IL-1β, IL-10 and CD68 did not change. Thus, in Balb/c mice from an enriched environment, there is no increase in the expression of BDNF and IL-10, which is typical for C57BL/6 mice, however, this does not prevent the proliferation and differentiation of neurons in the dentate gyrus and successful spatial orientation in the Barnes maze. Microglial cells in Balb/c mice under enriched conditions are probably polarized according to the M0/M2 type.