Long‐term environmental enrichment reduces microglia morphological diversity of the molecular layer of dentate gyrus

We investigated long‐term environmental influences on morphology of microglia from the outer and middle thirds of molecular layer of the dentate gyrus (MolDG), and on microglia from dorsal and ventral dentate gyrus molecular layer. We also estimated the total number of MolDG microglia using stereology. For this purpose, microglia of the molecular layer of the dentate gyrus of 20‐month‐old female Swiss albino mice, housed from 21st postnatal day onwards, in the impoverished environment of the standard laboratory cages (SEA), or in a cage with an enriched environment (EEA), were reconstructed microscopically in three dimensions and compared with each other and with microglia of 6‐month‐old female Swiss albino mice, also housed from weaning onwards in an enriched cage (EEY). All mice had their brains sectioned and processed for immunolabeling for IBA‐1, a selective microglia marker. Random and systematic microglia samples were reconstructed in three dimensions and classified morphologically using hierarchical cluster analysis, followed by discriminant function analysis. SEA and EEY showed two morphological phenotypes of microglia in both the outer and middle thirds of MolDG. EEA mice showed such a reduction in the morphological diversity of microglia that essentially a single morphotype was found. EEA mouse microglia showed an intermediate morphological complexity between types I and II SE microglia. We suggest that type I and type II microglia in SE mice may have different physiological roles and that long‐term EE may be associated with adaptive responses of microglial phenotypes to somatomotor and cognitive stimuli. Three‐dimensional reconstructions and corresponding dendrograms of type I and type II microglia of the middle (left) and external (right) thirds of the molecular layer of dentate gyrus of 20‐month‐old mice, maintained from weaning in standard cages (A and B) or in enriched cages (C). Type I and type II microglia in SE mice may have different physiological roles, and the reduction of EE microglia diversity may be an adaptive responses of microglial phenotypes to somatomotor and cognitive stimuli.