We have previously identified regions of the monkey brain that exhibit morphological signs of damage with age (i.e., subcortical nuclei, white matter ) and other regions that appear relatively well-preserved (i.e., cortical grey matter). The most striking observation is the significant loss of white matter and breakdown of myelin sheaths in the aged monkey brain. Breakdown of myelin may cause aberrant transfer of information leading to cognitive deficits. We hypothesize that some of this damage seen in the cognitively impaired monkeys may be caused by the action of activated astrocytes and microglia and the dysfunction of oligodendrocytes. The goal of this project is to examine morphologically, immunocytochemically and functionally the appearance of the activated glial cells, the induction or inhibition of expression of particular mRNAs, and the production of their related proteins in those regions of the aging brain that may be involved in neurodegeneration. This project will combine morphological and quantitative assessment of all three types of glial cells from young monkeys and compare them with similar assessments in successfully aging and cognitively impaired aging monkeys. We will also perform a functional analysis of the effect of age on these cells using freshly dissected brain slices. Specifically, we will analyze the expression of inflammation-related proteins such as cytokines, complement components and inducible nitric oxide synthase, which can be detrimental to various brain cells, among them the oligodendrocytes. Differential display of cDNAs amplified from specific brain regions will be used as a complementary technique to confirm the differential expression of genes for immune system and inflammatory proteins, and to identify novel genes that are differentially expressed in the three groups of monkeys. In situ hybridization will be used to localize the messages for these genes on a cellular level. As in all projects, the animals used will be categorized according to cognitive state, so that we can determine if changes in the neuroglial cell populations and their functions are related to cognitive decline.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Research Program Projects (P01)
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Boston University
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Robinson, Amy A; Abraham, Carmela R; Rosene, Douglas L (2018) Candidate molecular pathways of white matter vulnerability in the brain of normal aging rhesus monkeys. Geroscience 40:31-47
Ragan, I K; Davis, A S; McVey, D S et al. (2018) Evaluation of Fluorescence Microsphere Immunoassay for Detection of Antibodies to Rift Valley Fever Virus Nucleocapsid Protein and Glycoproteins. J Clin Microbiol 56:
Moore, Tara L; Bowley, Bethany G E; Shultz, Penny L et al. (2018) Oral curcumin supplementation improves fine motor function in the middle-aged rhesus monkey. Somatosens Mot Res 35:1-10
Medalla, Maria; Gilman, Joshua P; Wang, Jing-Yi et al. (2017) Strength and Diversity of Inhibitory Signaling Differentiates Primate Anterior Cingulate from Lateral Prefrontal Cortex. J Neurosci 37:4717-4734
Hsu, Alexander; Luebke, Jennifer I; Medalla, Maria (2017) Comparative ultrastructural features of excitatory synapses in the visual and frontal cortices of the adult mouse and monkey. J Comp Neurol 525:2175-2191
Shobin, Eli; Bowley, Michael P; Estrada, Larissa I et al. (2017) Microglia activation and phagocytosis: relationship with aging and cognitive impairment in the rhesus monkey. Geroscience 39:199-220
Estrada, Larissa I; Robinson, Amy A; Amaral, Ana C et al. (2017) Evaluation of Long-Term Cryostorage of Brain Tissue Sections for Quantitative Histochemistry. J Histochem Cytochem 65:153-171
Rumbell, Timothy H; Dragulji?, Danel; Yadav, Aniruddha et al. (2016) Automated evolutionary optimization of ion channel conductances and kinetics in models of young and aged rhesus monkey pyramidal neurons. J Comput Neurosci 41:65-90
Wilson, William C; Davis, A Sally; Gaudreault, Natasha N et al. (2016) Experimental Infection of Calves by Two Genetically-Distinct Strains of Rift Valley Fever Virus. Viruses 8:
Shivanna, Vinay; McDowell, Chester; Wilson, William C et al. (2016) Complete Genome Sequence of Two Rift Valley Fever Virus Strains Isolated from Outbreaks in Saudi Arabia (2000) and Kenya (2006 to 2007). Genome Announc 4:

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