Cannabinoid Receptor Type 1 (CB1R) Expression in Limbic Brain Structures After Acute and Chronic Seizures in a Genetic Model of Epilepsy

Autor(es)

Lazarini-Lopes, Willian ^{[1, 2]} ; da Silva-Junior, Rui M. P. ^{[3, 2]} ; Servilha-Menezes, Gabriel ^[2] ; Do Val-da Silva, Raquel A. ^[1] ; Garcia-Cairasco, Norberto ^{[1, 2]}

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Ribeirao Preto Sch Med, Neurosci & Behav Sci Dept, Ribeirao Preto - Brazil

^[2] Univ Sao Paulo, Ribeirao Preto Sch Med, Dept Physiol, Neurophysiol & Expt Neuroethol Lab, Ribeirao Preto - Brazil

^[3] Univ Sao Paulo, Ribeirao Preto Sch Med, Dept Internal Med, Ribeirao Preto - Brazil

• Tipo de documento: Artigo Científico
• Fonte: FRONTIERS IN BEHAVIORAL NEUROSCIENCE; v. 14, DEC 21 2020.
• Citações Web of Science: 0

Resumo

The endocannabinoid system (ECS) is related to several physiological processes, associated to the modulation of brain excitability, with impact in the expression of susceptibility and control of epileptic seizures. The cannabinoid receptor type 1 (CB1R) is widely expressed in the brain, especially in forebrain limbic structures. Changes in CB1R expression are associated with epileptic seizures in animal models and humans. The Wistar Audiogenic Rat (WAR) strain is a genetic model of epilepsy capable of mimicking tonic-clonic and limbic seizures in response to intense sound stimulation. The WAR strain presents several behavioral and physiological alterations associated with seizure susceptibility, but the ECS has never been explored in this strain. Therefore, the aim of the present study was to characterize CB1R expression in forebrain limbic structures important to limbic seizure expression in WARs. We used a detailed anatomical analysis to assess the effects of acute and chronic audiogenic seizures on CB1R expression in several layers and regions of hippocampus and amygdala. WARs showed increased CB1R immunostaining in the inner molecular layer of the hippocampus, when compared to control Wistar rats. Acute and chronic audiogenic seizures increased CB1R immunostaining in several regions of the dorsal hippocampus and amygdala of WARs. Also, changes in CB1R expression in the amygdala, but not in the hippocampus, were associated with limbic recruitment and limbic seizure severity in WARs. Our results suggest that endogenous alterations in CB1R immunostaining in WARs could be associated with genetic susceptibility to audiogenic seizures. We also demonstrated CB1R neuroplastic changes associated with acute and chronic seizures in the amygdala and hippocampus. Moreover, the present study brings important information regarding CB1R and seizure susceptibility in a genetic model of seizures and supports the relationship between ECS and epilepsy. (AU)

• Processo FAPESP: 19/00849-2 - Mecanismos fisiopatológicos e moleculares de tumorigênese: abordagem baseada em plataformas de sequenciamento em escala genômica (NGS - Next-generation sequencing)
• Beneficiário: Rui Milton Patrício da Silva Junior
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 19/02787-4 - Efeitos do canabidiol veiculado em nanoemulsão em ratos submetidos ao modelo químico de epilepsia do lobo temporal
• Beneficiário: Gabriel Servilha Menezes
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica
• Processo FAPESP: 14/50891-1 - INCT 2014: Translacional em Medicina
• Beneficiário: Jaime Eduardo Cecilio Hallak
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 19/05957-8 - Epilepsias e comorbidades neuropsiquiátricas: caracterização dos efeitos do tratamento com canabidiol e HUF-101 em modelos experimentais in vivo e in vitro
• Beneficiário: Norberto Garcia Cairasco
• Modalidade de apoio: Auxílio à Pesquisa - Regular