Abstract
Parkinson’s disease (PD) is characterized by the gradual degeneration of dopaminergic neurons in the substantia nigra, leading to striatal dopamine depletion. A partial unilateral striatal 6-hydroxydopamine (6-OHDA) lesion causes 40–60% dopamine depletion in the lesioned rat striatum, modeling the early stage of PD. In this study, we explored the connectivity between the brain regions in partially 6-OHDA lesioned male Wistar rats under urethane anesthesia using functional magnetic resonance imaging (fMRI) at 5 weeks after the 6-OHDA infusion. Under urethane anesthesia, the brain fluctuates between the two states, resembling rapid eye movement (REM) and non-REM sleep states. We observed clear urethane-induced sleep-like states in 8/19 lesioned animals and 8/18 control animals. 6-OHDA lesioned animals exhibited significantly lower functional connectivity between the brain regions. However, we observed these differences only during the REM-like sleep state, suggesting the involvement of the nigrostriatal dopaminergic pathway in REM sleep regulation. Corticocortical and corticostriatal connections were decreased in both hemispheres, reflecting the global effect of the lesion. Overall, this study describes a promising model to study PD-related sleep disorders in rats using fMRI.
Footnotes
The authors declare no competing financial interests.
This work was supported by Emil Aaltonen foundation (T.P.), Finnish Academy of Science and Letters (E.Z.), and the Academy of Finland (O.G.). The funding sources had no role in study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the article for publication. We thank Kalle Voutilainen for help with the animal experiments and DA assay, Maarit Pulkkinen for technical assistance in fMRI experiments, Jaana Leskinen for help with biochemical assays, Raimo Salo for valuable advice in data analysis, and Dr. Ewen MacDonald for the linguistic revision of this paper.
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