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

• Main Authors: Dario Carvalho-Paulo, João Bento Torres Neto, Carlos Santos Filho, Thais Cristina Galdino de Oliveira, Aline Andrade de Sousa, Renata Rodrigues dos Reis, Zaire Alves dos Santos, Camila Mendes de Lima, Marcus Augusto de Oliveira, Nivin Mazen Said, Sinara Franco Freitas, Marcia Consentino Kronka Sosthenes, Giovanni Freitas Gomes, Ediely Pereira Henrique, Patrick Douglas Côrrea Pereira, Lucas Silva de Siqueira, Mauro André Damasceno de Melo, Cristovam Guerreiro Diniz, Nara Gyzely de Morais Magalhães, José Antonio Picanço Diniz, Pedro Fernando da Costa Vasconcelos, Daniel Guerreiro Diniz, Daniel Clive Anthony, David Francis Sherry, Dora Brites, Cristovam Wanderley Picanço Diniz
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2021-06-01
• Series: Frontiers in Immunology
• Subjects: age and environment influence on microglia alteration; brain size and microglia response cognitive performances; Felsenstein’s independent phylogenetic contrast; microglia; mouse; bat
• Online Access: https://www.frontiersin.org/articles/10.3389/fimmu.2021.683026/full

Microglial immunosurveillance of the brain parenchyma to detect local perturbations in homeostasis, in all species, results in the adoption of a spectrum of morphological changes that reflect functional adaptations. Here, we review the contribution of these changes in microglia morphology in distantly related species, in homeostatic and non-homeostatic conditions, with three principal goals (1): to review the phylogenetic influences on the morphological diversity of microglia during homeostasis (2); to explore the impact of homeostatic perturbations (Dengue virus challenge) in distantly related species (Mus musculus and Callithrix penicillata) as a proxy for the differential immune response in small and large brains; and (3) to examine the influences of environmental enrichment and aging on the plasticity of the microglial morphological response following an immunological challenge (neurotropic arbovirus infection). Our findings reveal that the differences in microglia morphology across distantly related species under homeostatic condition cannot be attributed to the phylogenetic origin of the species. However, large and small brains, under similar non-homeostatic conditions, display differential microglial morphological responses, and we argue that age and environment interact to affect the microglia morphology after an immunological challenge; in particular, mice living in an enriched environment exhibit a more efficient immune response to the virus resulting in earlier removal of the virus and earlier return to the homeostatic morphological phenotype of microglia than it is observed in sedentary mice.