Age-related changes in regulator of G-protein signaling (RGS)-10 expression in peripheral and central immune cells may influence the risk for age-related degeneration

Neurobiol Aging. 2015 May;36(5):1982-93. doi: 10.1016/j.neurobiolaging.2015.02.006. Epub 2015 Feb 13.

Abstract

Inflammation in the aging brain increases risk for neurodegenerative disease. In humans, the regulator of G-protein signaling-10 (RGS10) locus has been associated with age-related maculopathy. Chronic peripheral administration of lipopolysaccharide in the RGS10-null mice induces nigral dopaminergic (DA) degeneration, suggesting that RGS10 modulates neuroimmune interactions and may influence susceptibility to neurodegeneration. Because age is the strongest risk factor for neurodegenerative disease, we assessed whether RGS10 expression changes with age and whether aged RGS10-null mice have altered immune cell profiles. Loss of RGS10 in aged mice does not alter the regulation of nigral DA neurons but does alter B-cell, monocyte, microglial, and CD4+ T-cell populations and inflammatory cytokine levels in the cerebrospinal fluid. These results suggest that loss of RGS10 is associated with an age-dependent dysregulation of peripheral and central immune cells rather than dysregulation of DA neuron function.

Keywords: Aging; Dopamine; Immune cells; Midbrain; Oxidative stress; RGS10; Tyrosine hydroxylase.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / genetics*
  • Aging / immunology*
  • Animals
  • B-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / immunology
  • Cerebrospinal Fluid / cytology
  • Cerebrospinal Fluid / immunology
  • Cytokines / cerebrospinal fluid
  • Dopaminergic Neurons
  • Female
  • Gene Expression / genetics*
  • Gene Expression / immunology*
  • Gene Expression Regulation, Developmental / genetics*
  • Gene Expression Regulation, Developmental / immunology*
  • Humans
  • Inflammation Mediators / cerebrospinal fluid
  • Male
  • Mice, Inbred C57BL
  • Microglia / immunology
  • Monocytes / immunology*
  • Nerve Degeneration / genetics*
  • Nerve Degeneration / immunology*
  • Neuroimmunomodulation / genetics*
  • Neuroimmunomodulation / immunology*
  • RGS Proteins / genetics*
  • RGS Proteins / metabolism*
  • Risk
  • Tyrosine 3-Monooxygenase / metabolism

Substances

  • Cytokines
  • Inflammation Mediators
  • RGS Proteins
  • Rgs10 protein, mouse
  • Tyrosine 3-Monooxygenase