Diurnal circadian clock gene expression is altered in models of genetic and acquired epilepsy

Author:

Yamakawa Glenn R.1,Patel Meshwa1,Lin Runxuan1ORCID,O'Brien Terence J.12,Mychasiuk Richelle1,Casillas‐Espinosa Pablo M.12ORCID

Affiliation:

1. Department of Neuroscience, Central Clinical School Monash University Melbourne Victoria Australia

2. Department of Neurology The Alfred Hospital Melbourne Victoria Australia

Abstract

AbstractObjectivesGrowing evidence demonstrates a relationship between epilepsy and the circadian system. However, relatively little is known about circadian function in disease states, such as epilepsy. This study aimed to characterize brain and peripheral core circadian clock gene expression in rat models of genetic and acquired epilepsy.MethodsFor the Genetic Absence Epilepsy Rats from Strasbourg (GAERS) study, we used 40 GAERS and 40 non‐epileptic control (NEC) rats. For the kainic acid status epilepticus (KASE) study, we used 40 KASE and 40 sham rats. Rats were housed in a 7 am:7 pm light–dark cycle. Hypothalamus, hippocampus, liver, and small intestine samples were collected every 3 h throughout the light period. We then assessed core diurnal clock gene expression of per1, cry1, clock, and bmal1.ResultsIn the GAERS rats, all tissues exhibited significant changes in clock gene expression (P < 0.05) when compared to NEC. In the KASE rats, there were fewer effects of the epileptic condition in the hypothalamus, hippocampus, or small intestine (P > 0.05) compared with shams.SignificanceThese results indicate marked diurnal disruption to core circadian clock gene expression in rats with both generalized and focal chronic epilepsy. This could contribute to epileptic symptomology and implicate the circadian system as a viable target for future treatments.

Funder

Department of Health and Aged Care, Australian Government

National Health and Medical Research Council

Publisher

Wiley

Subject

Neurology (clinical),Neurology

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