Detection of Early Neurochemical Changes Related to Neurodegeneration in a Spinocerebellar Ataxia Type 1 (SCA1) Mouse Model by 1H MRS at 9.4 Tesla

Uzay Emrah Emir¹, H Brent Clark¹, Manda Vollmers¹, Dee M. Koski¹, Lynn E. Eberly¹, Harry T. Orr¹, Huda Y. Zoghbi², Gulin Oz¹

In order to identify MRS biomarkers of very early neurochemical changes related to neurodegeneration, we utilized a knockin (KI) mouse model of SCA1. We measured cerebellar neurochemical profiles of KI mice and wild-type (WT) littermates longitudinally at 9.4T using short-echo LASER. Total choline, taurine and glutamine were the most robust biomarkers in this model. The KI mice displayed very mild cerebellar pathology even at 9 months, however they were distinguished from WTs by MRS starting at 6 weeks. Therefore, this study demonstrated that the MRS biomarkers are sensitive to very early changes related to neurodegeneration prior to overt pathology.