No detectable effect on visual responses using functional mri in a rodent model of a-synuclein expression

Abstract

Parkinson’s disease (PD) is a progressive neurodegenerative disease that is typically diagnosed late in its progression. There is a need for biomarkers suitable for monitoring the disease progression at earlier stages to guide the development of novel neuroprotective therapies. One potential biomarker, a-synuclein, has been found in both the familial cases of PD, as well as the sporadic cases and is considered a key feature of PD. a-synuclein is naturally present in the retina, and it has been suggested that early symptoms of the visual system may be used as a biomarker for PD. Here, we use a viral vector to induce a unilateral expression of human wild-type a-synuclein in rats as a mechanistic model of protein aggregation in PD. We employed functional magnetic resonance imaging (fMRI) to investigate whether adeno-associated virus (AAV) mediated expression of human wild-type a-synuclein alter functional activity in the visual system. A total of 16 rats were injected with either AAV-a-synuclein (n = 7) or AAV-null (n = 9) in the substantia nigra pars compacta (SNc) of the left hemisphere. The expression of a-synuclein was validated by a motor assay and post-mortem immunohistochemistry. Five months after the introduction of the AAV-vector, fMRI showed robust blood oxygen level-dependent (BOLD) responses to light stimulation in the visual systems of both control and AAV-a-synuclein animals. However, our results demonstrate that the expression of AAV-a-synuclein does not affect functional activation of the visual system. This negative finding suggests that fMRI-based read-outs of visual responses may not be a sensi-tive biomarker for PD.