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Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates
Published on: January 30, 2014
Increased microglial activation and protein nitration in white matter of the aging monkey
J A Sloane1, W Hollander, M B Moss
1Department of Pathology, Boston University School of Medicine, MA 02118, USA.
Abstract:
Activated microglia are important pathological features of a variety of neurological diseases, including the normal aging process of the brain. Here, we quantified the level of microglial activation in the aging rhesus monkey using antibodies to HLA-DR and inducible nitric oxide synthase (iNOS). We observed that 3 out of 5 white matter areas but only 1 of 4 cortical gray matter regions examined showed significant increases in two measures of activated microglia with age, indicating that diffuse white matter microglial activation without significant gray matter involvement occurs with age. Substantial levels of iNOS and 3-nitrotyrosine, a marker for peroxynitrite, increased diffusely throughout subcortical white matter with age, suggesting a potential role of nitric oxide in age-related white matter injury. In addition, we found that the density of activated microglia in the subcortical white matter of the cingulate gyrus and the corpus callosum was significantly elevated with cognitive impairment in elderly monkeys. This study suggests that microglial activation increases in white matter with age and that these increases may reflect the role of activated microglia in the general pathogenesis of normal brain aging.
Insights
Microglial activation increases in white matter during normal brain aging in rhesus monkeys. This age-related white matter microglial activation is linked to cognitive impairment and potential nitric oxide injury.
Area of Science:
- Neuroscience
- Neuropathology
- Aging Research
Background:
- Activated microglia are key in neurological diseases and normal brain aging.
- Microglial activation in aging brains is not fully understood, particularly its distribution in white vs. gray matter.
Purpose of the Study:
- To quantify microglial activation in the aging rhesus monkey brain.
- To investigate the association between microglial activation, aging, and cognitive function.
Main Methods:
- Used antibodies for HLA-DR and inducible nitric oxide synthase (iNOS) to measure microglial activation.
- Examined white matter and cortical gray matter regions in aging rhesus monkeys.
- Assessed levels of iNOS and 3-nitrotyrosine as markers of nitric oxide activity.
Main Results:
- Significant increases in microglial activation measures were found in white matter areas with age, but not consistently in gray matter.
- Age-related increases in iNOS and 3-nitrotyrosine were observed diffusely in subcortical white matter.
- Elevated activated microglia density in specific white matter regions correlated with cognitive impairment in elderly monkeys.
Conclusions:
- Microglial activation predominantly occurs in white matter during normal brain aging.
- Nitric oxide may play a role in age-related white matter injury.
- Increased white matter microglial activation is associated with cognitive decline in aging monkeys and may contribute to brain aging pathogenesis.
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