Hormonal Regulation of Sex Differences in Stress Effects in Prefrontal Cortex

前额皮质压力效应中性别差异的激素调节

• 批准号: 7991085
• 负责人: CARA L WELLMAN
• 金额: $ 7.61万
• 依托单位: TRUSTEES OF INDIANA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-06-24 至 2012-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7991085
• 关键词: Address; Amygdaloid structure; Androgens; Apical; Behavior; Behavioral; Castration; Chronic stress; Cognitive; Emotional; Estradiol; Female; Goals; Gonadal Hormones; Hippocampus (Brain); Hormonal; Hormones; Hypertrophy; Implant; Intervention; Length; Medial; Mediating; Mental Depression; Mental disorders; Morphology; Neurons; Ovariectomy; Pattern; Performance; Physiology; Post-Traumatic Stress Disorders; Prefrontal Cortex; Process; Pyramidal Cells; Rattus; Research; Role; Schizophrenia; Sex Characteristics; Stanolone; Stress; Structure; Testosterone; Woman; Work; base; emotion regulation; hippocampal pyramidal neuron; hormone regulation; implantation; male; men; motivated behavior; neurobiological mechanism; neurochemistry; prevent; public health relevance; public health research; research study; response; sex; stress related disorder

DESCRIPTION (provided by applicant): Stress can disrupt cognitive and emotional behavior and can precipitate or exacerbate many psychological disorders. Sex is an important variable influencing many stress-related disorders. Thus, understanding the basis of this sex difference is an important goal in developing appropriate interventions for stress-related disorders. Stress has profound effects on the morphology of corticolimbic structures including the hippocampus, amygdala, and prefrontal cortex. A growing body of work has documented sex differences in many behavioral, neurochemical, and morphological responses to stress. We have recently shown that chronic stress decreases the number and length of apical dendritic branches of pyramidal neurons in medial prefrontal cortex of male rats, but has the opposite effect in females, increasing apical dendritic length. We have further demonstrated that estradiol mediates this stress-induced dendritic hypertrophy in females: Both sham-operated and ovariectomized females with estradiol implants show stress-induced increases in apical dendritic material, whereas ovariectomy without estradiol replacement prevents the stress-induced increase. Interestingly, while ovariectomy without estradiol replacement prevented the stress-induced hypertrophy, it did not produce the male pattern of stress effects. This suggests that gonadal hormones may be permissive of stress-induced structural plasticity, but produce different effects in males and females, through either different hormones or different hormonal mechanisms. To more fully characterize potential sex differences in stress effects in mPFC, we will assess unit activity in the infralimbic cortex during performance on an emotion regulation task and dendritic morphology of pyramidal cells in the infralimbic cortex in stressed and unstressed male versus female rats. To determine whether gonadal hormones are permissive of the effects of chronic stress on structure and function of neurons in infralimbic cortex of males, we will assess unit activity in prefrontal cortex during performance on an emotion regulation task and dendritic morphology of pyramidal cells in infralimbic cortex in stressed and unstressed rats that have undergone castration and implantation of either no hormone, testosterone, dihydrotestosterone, or estradiol. To determine whether androgen administration can produce a male pattern of chronic stress effects on morphology and physiology of neurons in infralimbic cortex of females, we will assess unit activity in prefrontal cortex during performance on an emotion regulation task and dendritic morphology of pyramidal cells in infralimbic cortex in female stressed and unstressed rats that have undergone ovariectomy and implantation of either no hormone, testosterone, dihydrotestosterone, or estradiol. Results of the proposed studies will contribute to our understanding of the mechanisms underlying the sex difference seen in prefrontal stress effects. PUBLIC HEALTH RELEVANCE: This research will contribute to our understanding of the neurobiological mechanisms underlying sex differences in the influence of stress on emotional processing and negatively motivated behaviors. It will also aid in our understanding of how stress differentially influences mental illnesses such as posttraumatic stress disorder, depression, or schizophrenia in men and women.

描述（由申请人提供）：压力会破坏认知和情感行为，并加剧或加剧许多心理疾病。性别是影响许多与压力有关的疾病的重要变量。因此，理解这种性别差异的基础是开发与压力相关疾病的适当干预措施的重要目标。压力对包括海马，杏仁核和前额叶皮层在内的皮质脂质结构的形态具有深远的影响。越来越多的工作记录了许多行为，神经化学和形态学对压力的性别差异。我们最近表明，慢性应激减少了雄性大鼠内侧前额叶皮层中锥体神经元的顶端树突分支的数量和长度，但在女性中具有相反的作用，从而增加了顶端树突状长度。我们进一步证明，雌二醇介导这种压力诱导的女性树突状肥大：与雌二醇植入物的假手术和卵巢切除型女性均显示出根尖的树突状材料的压力诱导的增加，而没有雌激素替代的卵巢切除术会增加压力。有趣的是，虽然没有雌二醇替代的卵巢切除术阻止了压力引起的肥大，但它并未产生男性应激效应模式。这表明性腺激素可能允许应激诱导的结构可塑性，但通过不同的激素或不同的激素机制对男性和女性产生不同的影响。为了更充分地表征MPFC压力效应中潜在的性别差异，我们将在表现过程中评估肌状况的单位活性在情绪调节任务上，以及在压力和未育的男性和女性大鼠中，在压力性皮层中锥体细胞的树突形态。为了确定性腺激素是否允许慢性压力对男性临界皮层的结构和功能的影响睾丸激素，二氢睾丸激素或雌二醇。为了确定雄激素的给药是否可以产生女性的慢性压力对形态和神经元的生理影响的男性模式激素，睾丸激素，二氢睾丸激素或雌二醇。拟议研究的结果将有助于我们理解前额叶应力效应中性别差异的基础机制。 公共卫生相关性：这项研究将有助于我们对压力对情绪处理和负面动机行为影响的性别差异的神经生物学机制的理解。它还将有助于我们理解压力如何影响男性和女性的创伤后应激障碍，抑郁症或精神分裂症等精神疾病。