Sex differences in stress-induced dendritic remodeling

应激诱导的树突重塑的性别差异

• 批准号: 7294933
• 负责人: REBECCA M SHANSKY
• 金额: $ 4.88万
• 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/7294933
• 关键词: Address; Amygdaloid structure; Anxiety Disorders; Area; Atrophic; Basal Ganglia; Behavior; Behavioral; Biochemical; Biological; Brain region; Cells; Chronic; Chronic stress; Dendritic Spines; Disease; Electron Microscopy; Estrogen Replacements; Estrogens; Exposure to; Female; GABA Agonists; Hypertrophy; Infusion procedures; Investigation; Label; Learning; Major Depressive Disorder; Medial; Mediating; Memory; Mental disorders; Morphology; Muscimol; Names; Nature; Neurobiology; Neurons; Ovarian hormone; Pathology; Phobic anxiety disorder; Play; Post-Traumatic Stress Disorders; Prefrontal Cortex; Prevalence; Process; Rattus; Reporting; Role; Sex Characteristics; Site; Stress; Synapses; System; Techniques; Testing; Traumatic Stress Disorders; Vertebral column; Woman; acute stress; assault; base; biological adaptation to stress; lucifer yellow; male; men; prevent; retrograde transport; 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，这些区域已知保持相互连接。mPFC和杏仁核（BA）的基底核在应激暴露后发生形态学变化;有趣的是，虽然mPFC显示萎缩，但BA实际上报告为肥大。然而，尚不清楚这些变化是否发生在mPFC和杏仁核之间的神经元中。目前的建议，旨在探讨发生在BA投射神经元的mPFC暴露于慢性和急性应激后的形态学变化。我将进一步询问在这些变化中存在哪些性别差异，以及雌激素在介导这些差异中扮演什么角色（如果有的话）。为了了解参与这些过程的电路的本质，我将询问在应激期间蝇蕈醇诱导的杏仁核失活是否可以阻止mPFC中观察到的变化。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，并确定这些影响中性别差异的潜在位点。