Spinocerebellar ataxia type 1 (SCA1) is a fatal inherited neurodegenerative disease. In this study, we demonstrate the label-free optical imaging methodology that can detect, with a high degree of sensitivity, discrete areas of degeneration in the cerebellum of the SCA1 mouse models. We used ATXN1[82Q] and ATXN1[30Q]-D776 mice in which the transgene is directed only to Purkinje cells. Molecular layer, granular layer, and white matter regions are analyzed using the intrinsic contrasts provided by polarization-sensitive optical coherence tomography. Cerebellar atrophy in SCA1 mice occurred both in gray matter and white matter. While gray matter atrophy is obvious, indications of white matter atrophy including different birefringence characteristics, and shortened and contorted branches are observed. Imaging results clearly show the loss or atrophy of myelinated axons in ATXN1[82Q] mice. The method provides unbiased contrasts that can facilitate the understanding of the pathological progression in neurodegenerative diseases and other neural disorders.
Bibliographical noteFunding Information:
The work was supported by research grants from the US National Science Foundation (NSF, CBET-1510674 ) and the Bob Allison Ataxia Research Center (BAARC) at the University of Minnesota, as well as by the Graduate School Doctoral Dissertation Fellowship at the University of Minnesota (to C.J.L.). High-performance computing resources were provided by Minnesota Supercomputing Institute. The authors also would like to thank the late Jillian L. Friedrich for her constructive comments.
- Optical coherence tomography