Abstract
Microglia are the primary immune cells of the central nervous system that help nourish and support neurons, clear debris, and respond to foreign stimuli. Greatly impacted by their environment, microglia go through rapid changes in cell shape, gene expression, and functional behavior during states of infection, trauma, and neurodegeneration. Aging also has a profound effect on microglia, leading to chronic inflammation and an increase in the brain’s susceptibility to neurodegenerative processes that occur in Alzheimer’s disease. Despite the scientific community’s growing knowledge in the field of neuroinflammation, the overall success rate of drug treatment for age-related and neurodegenerative diseases remains incredibly low. Potential reasons for the lack of translation from animal models to the clinic include the use of a single species model, an assumption of similarity in humans, and ignoring contradictory data or information from other species. To aid in the selection of validated and predictive animal models and to bridge the translational gap, this review evaluates similarities and differences among species in microglial activation and density, morphology and phenotype, cytokine expression, phagocytosis, and production of oxidative species in aging and Alzheimer’s disease.
Highlights
Aβ plaques and vessels in aged orangutan (Pongo pygmaeus) brains were not associated with microglia activation [146]. These data demonstrate an important variance between humans and nonhuman primates (NHP). While both tau and Aβ are associated with increased microglial activation in Alzheimer’s disease (AD) brains, Aβ appears to be the predominant pathology correlated with neuroinflammation in NHP, perhaps due to significantly reduced neurofibrillary tangles (NFT) burden seen in these animals
Animal models for aging and neurodegenerative diseases range from bacteria to NHP, though the most common model is rodents
Rodents play a valuable role in biomedical research due to the ease of manipulating their genes, but scientists recognize the significant, evolutionary neurological differences between rodents and humans, which likely have contributed to high failure rates in AD clinical trials
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Anti-inflammatory cytokines, including IL-10, IL-4, and transforming growth factor-beta (TGF-β), downregulate activation of microglia and are neuroprotective [9,10] Another factor of the microglial phenotype is the expression of certain immunoepitopes to identify resting and activated states. Senescence in microglia is manifested by changes in density, activation, morphology, phenotype, cytokine expression, and phagocytosis [5,15,16] These age-associated changes produce persistent inflammation, making the brain increasingly susceptible to injury or neurodegeneration, and a broad range of research implicates microglia-mediated inflammatory processes as an important aspect in neurodegenerative diseases, such as Alzheimer’s disease (AD) [6,17,18,19,20]. We will highlight similarities and divergences among species in microglial activation, morphology and phenotype, cytokine expression, production of oxidative species, and phagocytosis
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