Sex differences in stress-induced dendritic remodeling

描述(由申请人提供)：女性患压力相关精神疾病的可能性是男性的两倍，如严重抑郁障碍(MDD)和创伤后应激障碍(PTSD)，但这种差异的生物学基础尚不清楚。这些疾病的特征通常是内侧前额叶皮质(MPFC)和杏仁核的活动和体积异常，这两个区域已知保持相互连接。应激暴露后，mPFC和杏仁核基底核(BA)都会发生形态变化；有趣的是，当mPFC显示萎缩时，BA实际上被报告为肥大。然而，尚不清楚这些变化是否发生在mPFC和杏仁核之间的投射神经元中。目前的建议试图探索在慢性和急性应激暴露后，mPFC内BA投射神经元的形态变化。我会进一步问，这些变化中存在哪些性别差异，如果有的话，雌激素在调节这些差异中扮演了什么角色。为了弄清参与这些过程的回路的本质，我将询问在应激过程中由蝇草醇诱导的杏仁核失活是否可以防止mPFC中出现的变化。总之，这些研究将有助于在细胞水平上确定应激对mPFC-BA回路的影响，以及确定这些影响中潜在的性别差异部位。

DESCRIPTION (provided by applicant): Women are twice as likely as men to develop stress-related mental illnesses like major depressive disorder (MDD) and post-traumatic stress disorder (PTSD), but the biological substrates of this discrepancy are unknown. These illnesses are frequently characterized by abnormalities in activity and volume of the medial prefrontal cortex (mPFC) and amygdala, regions known to maintain reciprocal connectivity. Both the mPFC and basal nucleus of the amygdala (BA) undergo morphological changes after stress exposure; interestingly, while the mPFC shows atrophy, the BA is in fact reported to hypertrophy. However, it is not known whether these changes occur in neurons that project between the mPFC and amygdala. The current proposal seeks to explore the morphological changes that occur in the BA-projecting neurons in the mPFC after exposure to both chronic and acute stress. I will further ask what sex differences exist in these changes, and what role, if any, estrogen plays in mediating such differences. To get at the nature of the circuitry involved in these processes, I will ask whether muscimol-induced inactivation of the amygdala during stress can prevent the changes seen in the mPFC. Together these studies will help to define the effects of stress on the mPFC-BA circuit at a cellular level, as well as identify potential sites of sex differences in these effects.