Department of Cellular and Physiological Sciences, The University of British Columbia , Vancouver, BC , Canada.
Department of Cellular and Physiological Sciences, The University of British Columbia , Vancouver, BC , Canada ; Department of Neuroscience, Carleton University , Ottawa, ON , Canada.
Front Endocrinol (Lausanne). 2014 Feb 13;5:5. doi: 10.3389/fendo.2014.00005. eCollection 2014.
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.
个体在妊娠期间接触酒精，表现出更高的精神病理学发生率。产前酒精暴露（PAE）引起的应激反应过度可能与这种精神病理学发生率的增加有关，尤其是因为该人群在一生中更有可能暴露于应激环境中。然而，酒精对压力和精神病理学表现的重叠神经回路的影响尚不完全清楚。在这里，我们对已知在情绪和应激调节中发挥关键作用的中枢区域内的神经活动进行了全面分析。来自 PAE、配对喂养和自由喂养对照组的成年雄性和雌性后代被暴露于慢性轻度应激（CMS）中。在 CMS 后，评估了杏仁核、腹侧海马结构、内侧前额叶皮质（mPFC）和下丘脑室旁核（PVN）的神经活动（c-fos mRNA）对急性应激（高架十字迷宫）的反应。我们的研究结果表明，总体而言，PAE 降低了雄性的杏仁核和海马结构内的神经活动，增加了雌性的杏仁核和 mPFC 内的神经活动。CMS 降低了 PAE 雄性的 mPFC 和 PVN 内的神经活动，但降低了对照组雄性中所有分析区域的活动。相比之下，CMS 降低了 PAE 雌性的 mPFC 中的神经活动，而对对照组雌性没有影响。此外，约束主成分分析表明，这些神经活动模式导致了雄性中功能性神经网络的激活与雌性不同，表明 PAE 和 CMS 具有性别二态性影响。重要的是，PAE 动物大脑激活的改变网络可能是产前接触酒精的个体表现出的应激反应过度和精神病理学增加的基础。
