Animal cells and systemsOct 17, 2026

Blocking REV-ERBα improves movement problems in a mouse model of Parkinson's disease

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Updated Oct 18, 2026

Abstract

Elevated Rev-erbα mRNA expression was found in tyrosine hydroxylase-positive neurons of the substantia nigra in a 6-hydroxydopamine mouse model of Parkinson's disease.

Circadian rhythm disturbances are commonly observed in Parkinson's disease patients.
The role of REV-ERBα in nigrostriatal dopamine regulation and motor function in Parkinson's disease is not fully understood.
Local administration of the REV-ERBα antagonist SR8278 improved motor performance and fine motor function in the mouse model.
These improvements occurred independently of the time of day.
SR8278 did not restore tyrosine hydroxylase expression or tissue dopamine levels in the striatum and substantia nigra.
In vivo microdialysis revealed increased extracellular dopamine turnover in the striatum, with higher levels of dopamine metabolites but unchanged basal dopamine levels.

Simplified

Parkinson's disease (PD) is characterized by nigrostriatal dopaminergic (DAergic) degeneration and motor dysfunction. Many PD patients also show circadian rhythm disturbances. Increasing evidence links circadian clock dysfunction to PD pathology. REV-ERBα is a circadian nuclear receptor that regulates DAergic genes under physiological conditions. However, its role in nigrostriatal dopamine (DA) homeostasis and motor function in PD remains unclear. In this study, we found elevated Rev-erbα mRNA expression in tyrosine hydroxylase (TH)-positive neurons of the substantia nigra (SN) in a 6-hydroxydopamine (6-OHDA) mouse model of PD. To test its functional role, we assessed the acute effects of local SN microinjection of the REV-ERBα antagonist SR8278. We found that SR8278 partially recovered motor performance and improved fine motor function. These effects occurred regardless of circadian timing. SR8278 administration did not restore TH expression or tissue DA levels in the striatum and SN. However, in vivo microdialysis showed enhanced extracellular DA turnover in the striatum. Specifically, while extracellular DA metabolites level increased, basal extracellular DA levels showed no change. Together, these findings identify REV-ERBα as a potential therapeutic target that modulates extracellular nigrostriatal DA dynamics and improves motor function in PD.

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Blocking REV-ERBα improves movement problems in a mouse model of Parkinson's disease

Abstract

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