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

Abstract

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.

BALB/c female subjected to valproic acid during gestational period exhibited greater microglial and behavioral changes than male mice: A significant contra intuitive result

“…Previous detailed information of immunolabeling procedure is available elsewhere (Shu et al. 1988, de Oliveira et al., 2020).…”

“…We estimated the total number of microglia using the optical fractionator (West et al., 1991). Detailed information of stereological procedures applied to the molecular layer of mouse dentate gyrus can be found elsewhere (de Oliveira et al., 2020).…”

Microglial Morphology Across Distantly Related Species: Phylogenetic, Environmental and Age Influences on Microglia Reactivity and Surveillance States

“…Based on three-dimensional reconstructions of microglia immunolabeled with antibodies for ionized calcium binding adaptor molecule 1 (Iba1), as a marker for microglia and macrophages across species (39), a comparative analysis of the three-dimensional morphometric features of microglia of dentate gyrus of C. pusilla (24), N. albiventris (unpublished results) and M. musculus (23), with correspondent 3D microglia reconstructions of the cell closest to the "mean cell" of each species is shown in Figure 1. To choose the representative mean cell of each species, we used the distance matrix (distance between microglia pairs) to obtain the sum of the distances of each cell in relation to all the others.…”

“…To search for morphological differences across phylogenetically distantly related species we reexamined our previous morphometric findings based on microglia three-dimensional reconstructions and compared data obtained in the dentate gyrus of mouse (Mus musculus) (23) and hippocampus V area of the semipalmated sandpiper (Calidris pusilla) (24), with those of microglia of the dentate gyrus of the lesser bulldog bat (Noctilio albiventris, unpublished results). The species selected allow the comparison of similar body weights and brain volumes for the microglia morphological categorization in the dentate gyrus, associated to contrasting locomotor and cognitive performances and distinct phylogenetic histories.…”

Microglia Function on Precursor Cells in the Adult Hippocampus and Their Responsiveness to Serotonin Signaling

“…As a result of positive stimuli, physical exercise, and ENR, altered microglia phenotypes display neuroprotective functions. In ENR, microglia morphology in adult rodent brain shows increased complexity in CA3 ( de Sousa et al, 2015 ) but decreased diversity in the molecular layer ( de Oliveira et al, 2020 ). In animal models for several diseases, physical activity induces anti-inflammatory effects revealed by decreased microglia activation and Iba-1/CD11b expression, a ramified morphology, or normalization in synaptic density in CA3 ( Andoh and Koyama, 2020 ).…”