Role of CCR3 in aging rhesus monkey brain
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Each year, aging and age-related deficits in cognitive function affect larger population worldwide. Research on aging has focused on changes in gray matter and white matter with age. A quantitative analysis of magnetic resonance images from healthy subjects of 16-79 years showed a significant negative correlation between gray matter volume and age (Taki et al., 2004). In addition, age-related cognitive decline is reported to be associated with white matter changes such as myelin damage, a result of both the inability of microglia to clear out damaged myelin debris and oligodendrocyte to support remyelination. Eotaxin-1 (CCL11) belongs to a group of eosinophil-specific chemoattractant originally found in peripheral immune system mediating allergic inflammation, asthma and atopic dermatitis (Garcia-Zepeda et al., 1996; Spergel, Mizoguchi, Oettgen, Bhan, & Geha, 1999). Recently it has been reported to have endogenous sources in the CNS and to increase with age in cerebral spinal fluid (CSF) as well as periphery in blood plasma. While CCL11 has been identified to increase with age, injection of CCL11 inhibit neurogenesis in young mice, which is likely to be mediated by C-C chemokine receptor type 3 (CCR3). CCR3 is also the only receptor for CCL11 that is expressed by oligodendrocyte precursor cells (OPCs) and by activated microglia in mice, which means it may participate in the process of microglial phagocytosis and oligodendrocyte myelination. To investigate if CCR3 is an important factor in the normal aging brain and its potential role in these existing findings, immunohistochemistry, stereology and densitometry were performed in the anterior cingulate cortex and cingulum from brain tissue of 4 young adults and 6 aged rhesus monkeys that were behaviorally tested previously to 1) demonstrate any association between CCR3 expression level and age 2) characterize changes in CCR3 level in relation to cognitive impairment 3) identify cellular localization of CCR3. We found a significant increase in amount of CCR3 cingulate cortex with age, which suggests its pro-disease effect in other pathways such as the interaction between CNS and T cell immune system. Although for aged group increase in CCR3+ cell density in white matter appeared insignificant, we found that CCR3 was expressed exclusively in OPCs but was absent in mature oligodendrocytes. indicating its role in OPC proliferation, oligodendrocyte maturation and myelination.
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