? ? The rhesus monkey is a model of normal human aging that enables testing age-related changes in brain physiology, neurochemistry and structure under carefully controlled conditions, thus avoiding confounding factors that obscure the sometimes subtle effects that aging has on the brain. The proposed study is a multimodal, cross-sectional MRI/MRS study that aims to detect age-related changes in the monkey brain. We will monitor microscopic and macroscopic structural parameters in the monkey brain using Diffusion Tensor Imaging (DTI), changes in volumetric measures using high-contrast/high resolution MRI anatomical images, as well as changes in the neurochemical profile of the monkey brain that can be non-invasively measured using Magnetic Resonance Spectroscopy (MRS). In this proposal we wish to perform a pilot multimodal MRI/MRS study on three age groups of rhesus monkeys (macaca mulatta). We wish to examine (1) reductions in frontal white matter (WM) diffusion anisotropy; (2) reductions in frontal gray matter volume; (3) changes in metabolite concentrations and in particular N-acetyl aspartate (NAA), myoinositol, choline, glutamine and GABA in frontal gray and white matter. These techniques will be used to perform a preliminary study on a small and well-controlled group of monkeys of both sexes. Following these studies, the monkeys will be sacrificed, and post-mortem analyses of brain tissue will be performed: (1) High resolution high-field NMR analysis of brain extracts; (2) histological observation of brain areas that appear to be affected according to the DTI and/or MR volumetric results.hese data will help us test the hypothesis that there is a solid MRI/MRS correlate of age-related cognitive deficits.
Our specific aims are: (1) Collection of preliminary data on the effects of aging on the monkey brain; (2) Validation of the MRI/MRS findings with post-mortem data on the same brains. ? ? ?
| Koo, Bang-Bon; Schettler, Steven P; Murray, Donna E et al. (2012) Age-related effects on cortical thickness patterns of the Rhesus monkey brain. Neurobiol Aging 33:200.e23-31 |
| Ronen, Itamar; Fan, Xiaoying; Schettler, Steve et al. (2011) Regional age-related effects in the monkey brain measured with 1H magnetic resonance spectroscopy. Neurobiol Aging 32:1138-48 |
