Magnetic Resonance Imaging and Spectroscopy of Rodent Models of Disease

National Institute On Aging

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Abstract

MR spectroscopy of brain is an excellent adjunct to morphologic imaging studies. We use this approach to define cerebellar metabolites in the XRCC1-deficient (KO) mouse, in which this key participant in base excision repair and single-strand break repair is lacking. Both MR imaging and spectroscopic analyses were performed. In the imaging experiments, cerebellar volume was found not to differ between the two groups. In the spectroscopy experiments, we were able to edit lipid signal by use of a TE = 135 ms, permitting clear delineation of choline, creatine, and NAA. No difference in the NAA neuronal marker was observed between the two groups. For both MRI volume measurements and MR spectroscopic measurements of neuronal viability, a larger variability in the data was seen in the XRCC1 KO animals. Overall, in spite of the cerebellar ataxia demonstrated in the XRCC1 KO phenotype, we found no differences in cerebellar volume or in cerebellar neuronal viability between the normal and KO animals. Thus, the ataxic phenotype is present in spite of preservation of these important parameters of brain phenotype. We will continue to refine our techniques and apply them to other disease models, such as Huntington's Chorea. Further work has evaluated chemogenetic stimulation of hypoglossal neurons in an investigation based on potential therapeutics for human sleep apnea. This work provides both a mechanistic basis as well as an insight in categories of therapeutic interventions that may be effective. We are continuing this analysis with further experiments involving animal models of disease. Further work involves studies of brain structural changes and cerebral blood flow in mouse models of Alzheimer's disease, and rat models of hypertension.