Application of MRS to mouse models of neurodegenerative illness

Abstract

The rapid development of transgenic mouse models of neurodegenerative diseases, in parallel with the rapidly expanding growth of MR techniques for assessing in vivo, non-invasive, neurochemistry, offers the potential to develop novel markers of disease progression and therapy. In this review we discuss the interpretation and utility of MRS for the study of these transgenic mouse and rodent models of neurodegenerative diseases such as Alzheimer's (AD), Huntington's (HD) and Parkinson's disease (PD). MRS studies can provide a wealth of information on various facets of in vivo neurochemistry, including neuronal health, gliosis, osmoregulation, energy metabolism, neuronal-glial cycling, and molecular synthesis rates. These data provide information on the etiology, natural history and therapy of these diseases. Mouse models enable longitudinal studies with useful time frames for evaluation of neuroprotection and therapeutic interventions using many of the potential MRS markers. In addition, the ability to manipulate the genome in these models allows better mechanistic understanding of the roles of the observable neurochemicals, such as N-acetylaspartate, in the brain. The argument is made that use of MRS, combined with correlative histology and other MRI techniques, will enable objective markers with which potential therapies can be followed in a quantitative fashion.