Non-invasive detection of neurochemical changes prior to overt pathology in a mouse model of spioncerebellar ataxia type 1

Spinocerebellar ataxia type 1 (SCA1) is a hereditary, progressive and fatal movement disorder that primarily affects the cerebellum. Non-invasive imaging markers to detect early disease in SCA1 will facilitate testing and implementation of potential therapies. We have previously demonstrated the sensitivity of neurochemical levels measured by H-1 magnetic resonance spectroscopy (MRS) to progressive neurodegeneration using a transgenic mouse model of SCA1. In order to investigate very early neurochemical changes related to neurodegeneration, here we utilized a knock-in mouse model, the Sca1(154Q/2Q) line, which displays milder cerebellar pathology than the transgenic model. We measured cerebellar neurochemical profiles of Sca1(154Q/2Q) mice and wild-type littermates using 9.4T MRS at ages 6, 12, 24, and 39weeks and assessed the cerebellar pathology of a subset of the mice at each time point. The Sca1(154Q/2Q) mice displayed very mild cerebellar pathology even at 39weeks, however, were distinguished from wild types by MRS starting at 6weeks. Taurine and total choline levels were significantly lower at all ages and glutamine and total creatine levels were higher starting at 12weeks in Sca1(154Q/2Q) mice than controls, demonstrating the sensitivity of neurochemical levels to neurodegeneration related changes in the absence of overt pathology.