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Pharmacological Rescue with SR8278, a Circadian Nuclear Receptor REV-ERBα Antagonist as a Therapy for Mood Disorders in Parkinson's Disease
Using a Drug That Blocks a Body Clock Protein to Treat Mood Problems in Parkinson's Disease
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Abstract
6-hydroxydopamine (6-OHDA)-lesioned mice exhibit increased depression- and anxiety-like behaviors specifically at dawn.
- Sundowning syndrome is linked to the emergence of neuropsychiatric symptoms at dusk in Parkinson's disease.
- The administration of REV-ERBα antagonist, SR8278, produced antidepressant and anxiolytic effects in a time-dependent manner.
- 6-OHDA lesions disrupted the transcription and binding activities of key nuclear receptors, REV-ERBα and NURR1, involved in dopamine regulation.
- SR8278 treatment restored REV-ERBα and NURR1 binding to the tyrosine hydroxylase promoter, leading to increased expression levels.
- Elevated tyrosine hydroxylase expression was observed in the ventral tegmental area of 6-OHDA-injected mice, particularly at dawn.
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