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

Spinocerebellar ataxia type 1 ( SCA 1) is a hereditary, progressive and fatal movement disorder that primarily affects the cerebellum. Non‐invasive imaging markers to detect early disease in SCA 1 will facilitate testing and implementation of potential therapies. We have previously demonstrated the sensitivity of neurochemical levels measured by 1 H magnetic resonance spectroscopy ( MRS ) to progressive neurodegeneration using a transgenic mouse model of SCA 1. 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 39 weeks 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 39 weeks, however, were distinguished from wild types by MRS starting at 6 weeks. Taurine and total choline levels were significantly lower at all ages and glutamine and total creatine levels were higher starting at 12 weeks in Sca1 154Q/2Q mice than controls, demonstrating the sensitivity of neurochemical levels to neurodegeneration related changes in the absence of overt pathology.We measured cerebellar neurochemical alterations in a knock‐in mouse model of spinocerebellar ataxia type 1, a hereditary movement disorder, using ultra‐high field magnetic resonance spectroscopy (MRS). Very early neurochemical alterations were detectable prior to overt pathology in the volume‐of‐interest for MRS. Alterations were indicative of osmolytic changes and of disturbances in membrane phospholipid and energy metabolism.