title: Age- and location-related changes in microglial function.
abstract: Inflammation in the central nervous system (CNS) is primarily regulated by microglia. No longer considered a homogenous population, microglia display a high degree of heterogeneity, immunological diversity and regional variability in function. Given their low rate of self-renewal, the microenvironment in which microglia reside may play an important role in microglial senescence. This study examines age-related changes in microglia in the brain and spinal cord. Using ex-vivo flow cytometry analyses, functional assays were performed to assess changes in microglial morphology, oxidative stress, cytokine production, and phagocytic activity with age in both the brain and spinal cord. The regional CNS environment had a significant effect on microglial activity with age. Blood-CNS barrier permeability was greater in the aging spinal cord compared with aging brain; this was associated with increased tissue cytokine levels. Aged microglia had deficits in phagocytosis at baseline and after stimulus-induced activation. The identification of age-specific, high scatter microglia together with the use of ex-vivo functional analyses provides the first functional characterization of senescent microglia. Age and regional-specificity of CNS disease should be taken into consideration when developing immune-modulatory treatments.
authors: Department of Neurology, University of Connecticut Health Center, Farmington, CT, USA.
authors: Rodney M
authors: RM
authors: Ritzel
authors: Department of Neurology, University of Connecticut Health Center, Farmington, CT, USA.
authors: Anita R
authors: AR
authors: Patel
authors: Department of Neurology, University of Connecticut Health Center, Farmington, CT, USA.
authors: Sarah
authors: S
authors: Pan
authors: Department of Neurology, University of Connecticut Health Center, Farmington, CT, USA.
authors: Joshua
authors: J
authors: Crapser
authors: Department of Neurology, University of Connecticut Health Center, Farmington, CT, USA.
authors: Matt
authors: M
authors: Hammond
authors: Department of Immunology, University of Connecticut Health Center, Farmington, CT, USA.
authors: Evan
authors: E
authors: Jellison
authors: Department of Neurology, University of Connecticut Health Center, Farmington, CT, USA. Electronic address: lmccullough@uchc.edu.
authors: Louise D
authors: LD
authors: McCullough
mesh_terms: D000375:Aging / Q000473:pathology* / Q000502:physiology*; D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism; D060833:Cellular Microenvironment / Q000502:physiology; D016922:Cellular Senescence / Q000502:physiology; D002490:Central Nervous System / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000276:immunology / Q000473:pathology* / Q000502:physiology*; D018384:Oxidative Stress; D010587:Phagocytosis
chemical_list: D016207:Cytokines
keywords: Aging; Heterogeneity; Inflammation; Microglia; Phagocytosis