Specific microglial phagocytic phenotype and decrease of lipid oxidation in white matter areas during aging: Implications of different microenvironments
| Autor: | Beatriz Almolda, Alex Perálvarez-Marín, Núria Benseny-Cases, Bernardo Castellano, Paula Sanchez-Molina, Berta González |
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| Rok vydání: | 2021 |
| Předmět: |
Male
0301 basic medicine Aging Transgene Mice Transgenic Biology White matter 03 medical and health sciences Myelin 0302 clinical medicine Phagocytosis Lipid oxidation medicine Animals Myelin Sheath Neuroinflammation Microglia Interleukin-6 General Neuroscience White Matter Phenotype Interleukin-10 Cell biology Mice Inbred C57BL 030104 developmental biology medicine.anatomical_structure Physiological Aging Cellular Microenvironment Female Lipid Peroxidation Neurology (clinical) Geriatrics and Gerontology 030217 neurology & neurosurgery Developmental Biology |
| Zdroj: | Neurobiology of Aging. 105:280-295 |
| ISSN: | 0197-4580 |
| Popis: | Physiological aging is characterized by an imbalance of pro-inflammatory and anti-inflammatory mediators leading to neuroinflammation. Microglial cells, which are highly regulated by the local microenvironment, undergo specific changes depending upon the brain area during aging. The aim of this study was to evaluate the influence of age over microglial cells along different brain areas and microenvironments. For this purpose, transgenic mice with overproduction of either the anti-inflammatory IL-10 cytokine or the pro-inflammatory IL-6 cytokine were used. Our results show that, during aging, microglial cells located in white matter (WM) areas maintain their phagocytic capacity but present a specific phagocytic phenotype with receptors involved in myelin recognition, arguing for aging-derived myelin damage. Whereas IL-10 overproduction anticipates the age-related microglial phagocytic phenotype, maintaining it over time, IL-6 overproduction exacerbates this phenotype in aging. These modifications were linked with a higher efficiency of myelin engulfment by microglia in aged transgenic animals. Moreover, we show, in a novel way, lower lipid oxidation during aging in WM areas, regardless of the genotype. The novelty of the insights presented in this study open a window to deeply investigate myelin lipid oxidation and the role of microglial cells in its regulation during physiological aging. |
| Databáze: | OpenAIRE |
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