Sex differences in stress-induced dendritic remodeling

应激诱导的树突重塑的性别差异

• 批准号: 7221343
• 负责人: REBECCA M SHANSKY
• 金额: $ 4.6万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-29 至 2009-09-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7221343
• 关键词: amygdala; behavior test; behavioral /social science research tag; dendrites; electron microscopy; estrogens; fluorescent dye /probe; gamma aminobutyrate; gender difference; hormone regulation /control mechanism; laboratory rat; muscimol; neuropathology; neuropharmacologic agent; ovariectomy; postdoctoral investigator; prefrontal lobe /cortex; psychological stressor; psychopathology; restraint; synaptogenesis

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.

描述（由申请人提供）：女性的可能性是男性发展与压力相关的精神疾病（如主要抑郁症（MDD）和创伤后应激障碍（PTSD））的可能性的两倍，但是这种差异的生物学基质尚不清楚。这些疾病通常以内侧前额叶皮层（MPFC）和杏仁核的活性和体积异常（已知维持相互连接性的区域）为特征。杏仁核（BA）的MPFC和基底核都会在压力暴露后发生形态变化。有趣的是，虽然MPFC显示出萎缩，但实际上据报道Ba为肥大。但是，尚不清楚这些变化是否发生在MPFC和杏仁核之间的神经元中。当前的提案试图探索暴露于慢性应激和急性应激后MPFC中BA射击神经元中发生的形态变化。我将进一步询问这些变化中存在哪些性别差异，以及雌激素在介导这种差异中的作用（如果有的话）。为了了解这些过程中涉及的电路的性质，我将询问马与压力期间杏仁核诱导的杏仁核的失活是否可以防止MPFC中看到的变化。这些研究一起将有助于定义压力对细胞水平上MPFC-BA电路的影响，并确定这些作用中性别差异的潜在位点。