Objective: In this study, we investigated the effects of SR9009, a Rev-ERB agonist, on the dopaminergic system in the MPTP model of PD.

Background: Circadian disturbance is a nonmotor complaint in Parkinson’s disease (PD) that manifests as changes in sleep-wake cycles, altered melatonin and cortisol secretion rhythms, and fluctuating blood pressure patterns. The molecular basis that links circadian rhythm and PD, however, is poorly understood.

Method: A subacute PD model was established by intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridyl (MPTP) in C57BL/6J mice. The specific agonist of Rev-erbα, SR9009, was administered intraperitoneally 7 days before and during MPTP administration. In this study, Pole test, rotation test and balance beam test were used to evaluate motor function. The survival of dopaminergic neurons in the substantia nigra and striatum was detected by immunohistochemistry and Nissl’s staining.

Results: The motor dysfunction (Figure 1) and loss of dopaminergic neurons( Figure 2) in the nigrostriatal system of MPTP mouse model were partially reversed by SR9009, a selective Rev-erbα agonist.

Conclusion: Collectively, our results suggest that activation of the circadian clock protein Rev-erbα plays an obligatory role in protecting dopaminergic neurons in PD, and Rev-erbα may be a therapeutic target for PD.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/pharmacological-activation-of-rev-erb%ce%b1-provides-neuroprotection-against-parkinsons-disease/