CNS-wide Sexually Dimorphic Induction of the Major Histocompatibility Complex 1 Pathway With Aging
| Autor: | Dustin R. Masser, Matthew M. Ford, Aditya Pisupati, David R. Stanford, Cory B. Giles, William E. Sonntag, Colleen A. Mangold, Georgina V. Bixler, Jonathan D. Wren, Willard M. Freeman |
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| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine Aging Central nervous system Major histocompatibility complex Major Histocompatibility Complex Synapse Mice 03 medical and health sciences Sex Factors 0302 clinical medicine Neuroplasticity medicine Animals Cellular localization Neuronal Plasticity biology Antigen processing Brain Mice Inbred C57BL 030104 developmental biology medicine.anatomical_structure Synaptic plasticity biology.protein Original Article Female Geriatrics and Gerontology Signal transduction Neuroscience 030217 neurology & neurosurgery Signal Transduction |
| Zdroj: | The Journals of Gerontology Series A: Biological Sciences and Medical Sciences. 72:16-29 |
| ISSN: | 1758-535X 1079-5006 |
| Popis: | The major histocompatibility complex I (MHCI) pathway, which canonically functions in innate immune viral antigen presentation and detection, is functionally pleiotropic in the central nervous system (CNS). Alternative roles include developmental synapse pruning, regulation of synaptic plasticity, and inhibition of neuronal insulin signaling; all processes altered during brain aging. Upregulation of MHCI components with aging has been reported; however, no systematic examination of MHCI cellular localization, expression, and regulation across CNS regions, life span, and sexes has been reported. In the mouse, MHCI is expressed by neurons and microglia, and MHCI components and receptors (H2-K1, H2-D1, β2M, Lilrb3, Klra2, CD247) display markedly different expression profiles across the hippocampus, cortex, cerebellum, brainstem, and retina. MHCI components, receptors, associated inflammatory transcripts (IL1α, IL1β, IL6, TNFα), and TAP (transporter associated with antigen processing) components are induced with aging and to a greater degree in female than male mice across CNS regions. H2-K1 and H2-D1 expression is associated with differential CG and non-CG promoter methylation across CNS regions, ages, and between sexes, and concomitant increased expression of proinflammatory genes. Meta-analysis of human brain aging data also demonstrates age-related increases in MHCI. Induction of MHCI signaling could contribute to altered synapse regulation and impaired synaptic plasticity with aging. |
| Databáze: | OpenAIRE |
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