Effect of multiple stresses during early-life on hyperthermia-induced epileptogenesis in young and adult mice

• Grant number: 12/21401-0
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: April 07, 2013
• End date: April 06, 2014
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Norberto Garcia Cairasco
• Grantee: Eduardo Henrique de Lima Umeoka
• Supervisor: Marian Joëls
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Institution abroad: Utrecht University (UU), Netherlands
• Associated to the scholarship: 11/13412-0 - Behavioral and morphologic characterization related to hypothalamic-pituitary-adrenal (HPA) axis activity in Wistar audiogenic rats after chronic seizures, BP.DR

Abstract

Epilepsy affects about 1% of world population according to WHO, and temporal lobe epilepsy (TLE) is the most common form of epilepsy in adults (Pitkänen, 2007). Febrile seizures (FS) are the most frequent type of convulsions in infants and young children, occurring in 2-6% of children (Nelson & Ellenberg 1976; Stafstrom, 2002). Long duration FS have been associated with subsequent TLE as indicated from retrospective studies (Cendes et al., 1993; Berg & Shinnar, 1996; Chen et al., 1999; French et al., 1993), as well as from recent data in animal models (Dubé et al., 2000, 2010).Early life adversity is a major risk factor for the development of many brain disorders, including epilepsy (Van Campen et al., 2012). In patients with epilepsy, stress is one of the most frequently self-reported precipitants for seizures (Frucht et al., 2000; Nakken et al., 2005; Lunardi et al., 2011). There are several evidences of the role of stress on seizures development in many experimental models of epilepsy, especially TLE (Joëls, 2009).We believe that the study of association between experimental model of FS and early-life stress will help us to elucidate the factors and mechanisms involved on the epileptogenesis process, and clarify how stress influence this phenomenon.For this purpose we will induce long lasting febrile seizures in mice during early-life (PND10) and submit the animals to multiple stresses protocol during the following 14 days. Effects of hyperthermia and multiple stresses on HPA axis activity will be evaluated through plasmatic measurements of corticosterone and in situ hybridization for GR, MR and CRH-R. Effects of early-life adversities, after hyperthermia-induced seizures, on epileptogenesis and neurogenesis will be evaluated through behavioral and EEG analyses of spontaneous recurrent seizures, and specific immunological markers, respectively. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

UMEOKA, EDUARDO H. L.; ROBINSON, EDWARD J.; TURIMELLA, SADA LAKSHMI; VAN CAMPEN, JOLIEN S.; MOTTA-TEIXEIRA, LIVIA C.; SARABDJITSINGH, R. ANGELA; GARCIA-CAIRASCO, NORBERTO; BRAUN, KEES; DE GRAAN, PIERRE N.; JOELS, MARIAN. Hyperthermia-induced seizures followed by repetitive stress are associated with age-dependent changes in specific aspects of the mouse stress system. Journal of Neuroendocrinology, v. 31, n. 4, APR 2019. (16/18941-4, 11/13412-0, 12/21401-0)