Sex differences in stress-induced dendritic remodeling

描述（由申请人提供）：女性患与压力有关的精神疾病的可能性是男性的两倍，如重度抑郁症（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。这些疾病通常以内侧前额叶皮层（mPFC）和杏仁核的活动和体积异常为特征，这些区域已知维持相互连接。应激后mPFC和杏仁核基底核（BA）均发生形态学改变；有趣的是，当mPFC显示萎缩时，BA实际上被报道为肥大。然而，目前尚不清楚这些变化是否发生在mPFC和杏仁核之间的神经元上。目前的建议旨在探索在暴露于慢性和急性应激后，mPFC中ba投射神经元发生的形态学变化。我将进一步问，在这些变化中存在什么性别差异，如果有的话，雌激素在调节这种差异中起什么作用。为了了解这些过程中所涉及的电路的本质，我将问，在压力下，肌肉醇引起的杏仁核失活是否可以防止在mPFC中看到的变化。总之，这些研究将有助于在细胞水平上确定压力对mPFC-BA回路的影响，并确定这些影响中潜在的性别差异。

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.