The Expression and Effects of Rev-Erbα in Different Cerebral Regions of Mice With Acute and Chronic Epilepsy

Epileptic seizures exhibit distinct circadian rhythms. Disruption of this rhythm creates a vicious cycle that further exacerbates the seizures. Rev-Erbα is a key circadian regulator that plays a significant role in epilepsy. In this study we aimed to investigate the expression and effects of Rev-Erbα and its agonist SR9009 across different brain regions during acute status epilepticus (SE) and chronic epilepsy (CE).

C57BL/6J mice were randomly divided into control, epilepsy (SE and CE), and SR9009+epilepsy (SR9009-E) groups. The distribution and expression of Rev-Erbα in the medial prefrontal cortex (mPFC), hippocampus (HP), and occipital visual cortex (V2M) of mice with SE and CE mice were detected using immunofluorescence and western blotting. Electroencephalography (EEG), the open-field test, and the Y-maze test were applied to evaluate epileptic activity, anxiety, and spatial memory.

Rev-Erbα expression differed significantly across cerebral regions among the control, epilepsy (SE and CE), and the SR9009-E groups (p < 0.05). SR9009-E mice had fewer seizures and less abnormal EEG discharge (p < 0.05) and showed better behavioral outcomes, including reduced anxiety-related behaviors and improved spatial memory, compared with epileptic mice (p < 0.05). Immunofluorescence showed higher neuronal numbers in the SR9009-E group than in the epilepsy group (p < 0.05).

Rev-Erbα dysregulation is tightly linked to epilepsy progression. Activation of Rev-Erbα exerts antiepileptic and neuroprotective effects and improves epilepsy-related neurobehavioral deficits, thereby offering a novel strategy for epilepsy treatment.