title: Neurocircuitry underlying stress and emotional regulation in animals prenatally exposed to alcohol and subjected to chronic mild stress in adulthood.
abstract: Individuals exposed to alcohol during gestation show higher rates of psychopathologies. The hyperresponsivity to stress induced by prenatal alcohol exposure (PAE) may be related to this increased rate of psychopathologies, especially because this population is more likely to be exposed to stressful environments throughout life. However, alcohol-induced changes in the overlapping neurocircuitries that underlie stress and the expression of psychopathologies are not fully understood. Here, we performed a comprehensive analysis of the neural activity within central areas known to play key roles in both emotional and stress regulation. Adult male and female offspring from PAE, pair-fed, and ad libitum-fed control conditions were exposed to chronic mild stress (CMS). Following CMS, the neural activity (c-fos mRNA) of the amygdala, ventral hippocampal formation, medial prefrontal cortex (mPFC), and paraventricular nucleus of hypothalamus (PVN) was assessed in response to an acute stress (elevated plus maze). Our results demonstrate that, overall, PAE decreased neural activity within the amygdala and hippocampal formation in males and increased neural activity within the amygdala and mPFC in females. CMS reduced neural activity within the mPFC and PVN in PAE males, but reduced activity in all areas analyzed in control males. By contrast, CMS reduced neural activity in the mPFC in PAE females and had no effects in control females. Furthermore, the constrained principal component analysis revealed that these patterns of neural activity resulted in differential activation of the functional neural networks in males compared to females, indicating sexually dimorphic effects of PAE and CMS. Importantly, the altered networks of brain activation in PAE animals may underlie the hyperresponsivity to stress and increased psychopathologies observed among individuals prenatally exposed to alcohol.
authors.affiliation: Department of Cellular and Physiological Sciences, The University of British Columbia , Vancouver, BC , Canada.
authors.forename: Charlis
authors.initials: C
authors.lastname: Raineki
authors.affiliation: Department of Cellular and Physiological Sciences, The University of British Columbia , Vancouver, BC , Canada ; Department of Neuroscience, Carleton University , Ottawa, ON , Canada.
authors.forename: Kim G C
authors.initials: KG
authors.lastname: Hellemans
authors.affiliation: Department of Cellular and Physiological Sciences, The University of British Columbia , Vancouver, BC , Canada.
authors.forename: Tamara
authors.initials: T
authors.lastname: Bodnar
authors.affiliation: Department of Psychiatry, The University of British Columbia , Vancouver, BC , Canada ; BC Mental Health and Addictions Research Institute (BCMHARI) , Vancouver, BC , Canada.
authors.forename: Katie M
authors.initials: KM
authors.lastname: Lavigne
authors.affiliation: Department of Cellular and Physiological Sciences, The University of British Columbia , Vancouver, BC , Canada.
authors.forename: Linda
authors.initials: L
authors.lastname: Ellis
authors.affiliation: Department of Psychiatry, The University of British Columbia , Vancouver, BC , Canada ; BC Mental Health and Addictions Research Institute (BCMHARI) , Vancouver, BC , Canada.
authors.forename: Todd S
authors.initials: TS
authors.lastname: Woodward
authors.affiliation: Department of Cellular and Physiological Sciences, The University of British Columbia , Vancouver, BC , Canada.
authors.forename: Joanne
authors.initials: J
authors.lastname: Weinberg
keywords: amygdala; c-fos; chronic mild stress; constrained principal component analysis; hippocampus; paraventricular nucleus of hypothalamus; prefrontal cortex; prenatal alcohol exposure