title: Pilocarpine-induced epilepsy alters the expression and daily variation of the nuclear receptor RORα in the hippocampus of rats.
abstract: It is widely known that there is an increase in the inflammatory responses and oxidative stress in temporal lobe epilepsy (TLE). Further, the seizures follow a circadian rhythmicity. Retinoic acid receptor-related orphan receptor alpha (RORα) is related to anti-inflammatory and antioxidant enzyme expression and is part of the machinery of the biological clock and circadian rhythms. However, the participation of RORα in this neurological disorder has not been studied. The aim of this study was to evaluate the RORα mRNA and protein content profiles in the hippocampus of rats submitted to a pilocarpine-induced epilepsy model at different time points throughout the 24-h light-dark cycle analyzing the influence of the circadian rhythm in the expression pattern during the acute, silent, and chronic phases of the experimental model. Real-time PCR and immunohistochemistry results showed that RORα mRNA and protein expressions were globally reduced in both acute and silent phases of the pilocarpine model. However, 60days after the pilocarpine-induced status epilepticus (chronic phase), the mRNA expression was similar to the control except for the time point 3h after the lights were turned off, and no differences were found in immunohistochemistry. Our results indicate that the status epilepticus induced by pilocarpine is able to change the expression and daily variation of RORα in the rat hippocampal area during the acute and silent phases. These findings enhance our understanding of the circadian pattern present in seizures as well as facilitate strategies for the treatment of seizures.
authors.affiliation: Department of Neurology and Neurosurgery, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil.
authors.forename: Anna Karynna Alves de Alencar
authors.initials: AK
authors.lastname: Rocha
authors.affiliation: Department of Neurology and Neurosurgery, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil; Department of Physiology and Biophysics, Institute of Biomedical Science, Universidade de São Paulo, São Paulo, SP, Brazil.
authors.forename: Eliangela
authors.initials: E
authors.lastname: de Lima
authors.affiliation: Department of Physiology and Biophysics, Institute of Biomedical Science, Universidade de São Paulo, São Paulo, SP, Brazil. Electronic address: fgamaral@gmail.com.
authors.forename: Fernanda Gaspar
authors.initials: FG
authors.lastname: do Amaral
authors.affiliation: Department of Physiology and Biophysics, Institute of Biomedical Science, Universidade de São Paulo, São Paulo, SP, Brazil.
authors.forename: Rafael
authors.initials: R
authors.lastname: Peres
authors.affiliation: Department of Physiology and Biophysics, Institute of Biomedical Science, Universidade de São Paulo, São Paulo, SP, Brazil.
authors.forename: José
authors.initials: J
authors.lastname: Cipolla-Neto
authors.affiliation: Department of Neurology and Neurosurgery, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil.
authors.forename: Débora
authors.initials: D
authors.lastname: Amado
mesh_terms: D000818:Animals; D002908:Chronic Disease; D002940:Circadian Rhythm / Q000235:genetics; D004827:Epilepsy / Q000139:chemically induced* / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D018721:Muscarinic Agonists; D057094:Nuclear Receptor Subfamily 1, Group F, Member 1 / Q000096:biosynthesis* / Q000235:genetics*; D010862:Pilocarpine; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D013226:Status Epilepticus / Q000139:chemically induced / Q000235:genetics
chemical_list: D018721:Muscarinic Agonists; D057094:Nuclear Receptor Subfamily 1, Group F, Member 1; D012333:RNA, Messenger; C000598704:Roralpha protein, rat; D010862:Pilocarpine
keywords: Epilepsy; Pilocarpine; RORα receptor