Evaluating a Label-Free Method for Quantifying Cerebellar Changes in a Mouse Model of SCA8

Acknowledgements In the past, in order to accurately visualize the mouse brain for quantitative measurement, time and resource intensive staining methods, such as Nissl or immunofluorescence, have been required (1,2). A newly developed labelfree method using the Serial Optical Coherence Scanner (SOCS) has the potential to dramatically reduce the time required to prepare brain samples for analysis by utilizing the natural differences in the way white and grey matter scatter light to produce an accurate image from which numerous quantitative measurements can be taken (3,4,5). In order to establish that SOCS can be used for the same precision of analysis that can be performed using immunohistochemistry in measurements including cerebellar area/volume as well as differentiation and measurement of the main layers of the cerebellum, we utilized a mouse model predicted to have notable deficits in these areas. A mouse model of Spinocerebellar ataxia type 8 (SCA8) has been documented to exhibit cerebellar Purkinje Cell death, which can be expected to thin the molecular layer, as well as demyelination, which would manifest in a decreased amount of cerebellar white matter (6,7). A profound cerebellar atrophy has been observed in multiple MRI studies of human SCA8 patients (8, 9). Together these instances of cell death and evidence from human patients should result in a measurable difference in area between SCA8 and wild type (WT) animals. In this small preliminary study, we wanted to determine if the SOCS method could be employed to parse out any difference in overall cerebellar area and molecular layer thickness between SCA8 and age matched WT mice.