Chronic Prenatal Ethanol Exposure Alters Glucocorticoid Signalling in the Hippocampus of the Postnatal Guinea Pig

Abstract

The present study tested the hypothesis that chronic prenatal ethanol exposure causes long-lasting changes in glucocorticoid signalling in postnatal offspring. Pregnant guinea pigs were treated with ethanol (4 g/kg maternal body weight/day), isocaloric-sucrose/pair-feeding or water throughout gestation, and maternal saliva cortisol concentration was determined 2 h after treatment at different stages of gestation. Electrically-stimulated release of glutamate and GABA, in the presence or absence of dexamethasone, as well as glucocorticoid and mineralocorticoid receptor mRNA expression, was determined in the hippocampus and prefrontal cortex of adult offspring of treated pregnant guinea pigs. Maternal saliva cortisol concentration increased throughout pregnancy, which was associated with increased foetal plasma and amniotic fluid cortisol concentration. Ethanol administration to pregnant guinea pigs increased maternal saliva cortisol concentration during early and mid-gestation. In late gestation, ethanol administration did not increase saliva cortisol concentration above that induced by pregnancy. Chronic prenatal ethanol exposure had no effect on stimulated glutamate or GABA release, but selectively prevented dexamethasone-mediated suppression of stimulated glutamate release, and decreased expression of mineralocorticoid, but not glucocorticoid, receptor mRNA in the hippocampus of adult offspring. These data indicate that maternal ethanol administration leads to excessively increased maternal cortisol concentration that can impact negatively the developing foetal brain, leading to persistent postnatal deficits in glucocorticoid regulation of glutamate signalling in the adult hippocampus.

Effects of prenatal alcohol exposure on hippocampal volume, verbal learning, and verbal and spatial recall in late childhood

“…Finally, as is typical in studies of FASDs, our FASD group differed from controls on several environmental factors that may have adversely affected their cognitive and socioemotional development in ways we were unable to detect in the present study. For instance, the effects of PAE on hippocampal development and the acquisition of specific cognitive skills may have been further exacerbated by factors such as exposure to cigarettes or cocaine during pregnancy, early physical abuse or neglect, living in foster care, a diagnosis of ADHD, lower family income, lower birth weight, maternal stress, and poor prenatal care (Iqbal et al, 2005;May & Gossage, 2001;Zhang et al, 2005).…”

Neural Connectivity in the Mediobasal Hypothalamus of the Sheep Brain

“…– rabbit polyclonal antibody against NPY (1:1,000, courtesy of Dr. A. Lawrence, Monash University, Melbourne, Australia) [27, 30, 31],…”

“…– rabbit polyclonal antibody against somatostatin (SRIH, 1:2,000, courtesy of Dr. J. Oliver, Flinders Medical Centre, Adelaide, Australia) [31,32,33],…”

“…– mouse monoclonal antibody against enkephalin (ENK, 1:1,000) (Chemicon, Temecula, Calif., USA) [31, 36, 37],…”

Exposição gestacional ao etanol e avaliação de níveis de cortisol salivar em crianças em idade escolar

“…Ademais, a exposição pré-natal ao álcool alterou o desenvolvimento do eixo L-HPA (Eixo límbico hipofisario adrenal), dando como consequência a recuperação lenta de hormônios do estresse em ratos (IQBAL et al, 2005), e macacos (SCHNEIDER et al, 2004;WEINBERG, 2008 A administração de álcool tem uma influência significativa quando é exposto conjuntamente ao estresse, já que a exposição de álcool durante a primeira semana ou terceira de gestação, altera a resposta hipotálamo-pituitária-adrenal e se observa um aumento significativo no CRF (biossíntese e expressão), que pode ser em parte consequência de elevados níveis do corticosterona circulante (LEE et al, 1990 …”