Sex and Region-Specific Impact of a Low-Protein Diet and Environmental Enrichment on Microglial IBA1 Expression in the Hippocampus of Mouse Offspring

Maternal protein malnutrition has lasting effects that negatively impact brain development and offspring behavior, increasing the risk of anxiety and depression. It has been described that malnutrition increases the risk of a dysregulated immune response leading to neuroinflammation, but little is known about the role of glial cells in response to early-life adversities nor the effect of environmental enrichment on the glial response. In this study, we examined the IBA1+ area in the hippocampus of female and male mouse offspring exposed to a low-protein (8% casein, LP) or normal-protein diet (20% casein, NP) during gestation and lactation until P21. We performed IHC for IBA1 in free-floating sections and analyzed the mean intensity and area of the staining in the hilus and molecular layer of the hippocampus. Results in male offspring at P21 showed a smaller IBA1+ area and higher IBA1 intensity in the LP-group compared to the NP group in both analyzed regions. No significant differences in IBA1 expression were observed in either region in female offspring, nor in maternal IBA1 expression. We extended the analysis to P56 offspring, where a subset of the LP-group was exposed to an enriched environment (LP-EE) to assess whether EE could reverse the effects of perinatal malnutrition. Since EE reversed anxiety-like behavior in previous behavioral assays, we aim to determine whether these restorative effects are also reflected in hippocampal microglia.