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Behavioral and morphologic characterization related to hypothalamic-pituitary-adrenal (HPA) axis activity in Wistar audiogenic rats after chronic seizures

Grant number: 11/13412-0
Support Opportunities:Scholarships in Brazil - Doctorate
Effective date (Start): October 01, 2011
Effective date (End): March 31, 2015
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Norberto Garcia Cairasco
Grantee:Eduardo Henrique de Lima Umeoka
Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Associated scholarship(s):12/21401-0 - Effect of multiple stresses during early-life on hyperthermia-induced epileptogenesis in young and adult mice, BE.EP.DR


Previous studies in our laboratory show that Wistar Audiogenic rats (WARs) present important differences in the hypothalamic-pituitary-adrenal (HPA) axis activity when compared to Wistar rats. These differences include adrenal gland morphometric and histopathology alterations, difference in the corticosterone and ACTH release pattern after both restrain stress and CRF injection, and during the circadian variation (Umeoka et al., 2011). Chronic seizures protocol promote the recruitment of limbic structures (Kiesmann et. al., 1988; Hirsch et. al., 1992; Garcia-Cairasco et. al., 1996) and this process is known as audiogenic kindling and indirectly activates the hypothalamic-pituitary system (Eells et al., 2004) through the amygdala and hippocampus (Hirsch et. al., 1992; Dutra Moraes et al, 2000; Romcy-Pereira & Garcia-Cairasco, 2003). A convulsive seizure promotes the activation of the HPA axis that leads to an increase in plasmatic glucocorticoid levels. Several studies have demonstrated the glucocorticoid role in the modulation of neuronal excitability (Kraulis et. al., 1975) and seizures susceptibility, in both acute and chronic epilepsy models (Kling et. al., 1993; Roberts & Keith, 1995; Castro et. al., 2010). Epileptic seizures can also promote neurogenesis especially in the dentate gyrus (Parent et. al., 1997). Our laboratory showed that after a chronic protocol of audiogenic seizures WARs had increased neurogenesis (Romcy-Pereira & Garcia-Cairasco, 2003).The objective of this Project is to seek a better understanding of HPA axis role in the generation and modulation of seizures susceptibility in WARs. Once WARs did not present ACTH circadian release (Umeoka et al., 2011), the expression of audiogenic kindling will be verified during the night. Moreover, we are going to determine which brain nuclei will be activated after audiogenic kindling through immunohistochemistry technique for c-Fos protein. The participation of corticosterone and their receptors will be evaluated, as well, in the modulation of chronic seizures in WARs. Finally, will be verified also, how the chronic restraint stress would modify the neurogenesis induced by audiogenic kindling and the newborn neurons morphology. (AU)

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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, . (16/18941-4, 11/13412-0, 12/21401-0)

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