The Role of Genetic Sex in Affect Regulation

遗传性别在情感调节中的作用

• 批准号: 8932026
• 负责人: Marianne L Seney
• 金额: $ 15.64万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-26 至 2017-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8932026
• 关键词: Adult; Affect; Agonist; Alzheimer' s Disease; Androgen Receptor; Anti-Anxiety Agents; Antidepressive Agents; Anxiety; Anxiety Disorders; Autopsy; Behavior; Behavioral; Behavioral Mechanisms; Bioinformatics; Biological; Bipolar Depression; Brain; Brain Diseases; Brain region; Cell physiology; Cells; Chronic stress; Clinical; D Cells; Data Set; Dendrites; Designer Drugs; Development; Discipline; Disease; Environment; Enzymes; Equilibrium; Estradiol; Estrogen Receptors; Etiology; Exposure to; Feedback; Female; Functional disorder; Funding; Gender; Gene Proteins; Gene Transfer; Genes; Genetic; Genotype; Glutamate Decarboxylase; Glutamates; Grant; Health; Hormones; Human; Individual; Institution; Knowledge; Lead; Learning; Link; Location; Major Depressive Disorder; Mass Spectrum Analysis; Mediating; Mental Depression; Mentors; Mentorship; Messenger RNA; Methods; Molecular; Mood Disorders; Mus; Neuroendocrinology; Neurons; Neuropeptides; Outcome; Pathway interactions; Pharmacogenetics; Population; Prevalence; Prevention; Proteins; Proteomics; Psychiatry; Regulation; Reporting; Research; Research Personnel; Risk; Rodent; Rodent Model; Role; Schizophrenia; Sex Characteristics; Sex Chromosomes; Sex Functioning; Signal Transduction; Somatostatin; Specificity; Techniques; Testosterone; Training; Universities; Viral; Viral Vector; Woman; anxiety-like behavior; base; behavioral outcome; brain cell; cell type; depressive symptoms; effective therapy; experience; frontal lobe; gamma-Aminobutyric Acid; genetic variant; hippocampal pyramidal neuron; inhibitory neuron; insight; male; men; novel; programs; protective effect; receptor; sex; sexual dimorphism; skills; translational approach

DESCRIPTION (provided by applicant): Somatostatin, a neuropeptide expressed in a subset of inhibitory neurons in the brain, is decreased in humans across multiple brain disorders, including schizophrenia, bipolar depression and Alzheimer's disease. Somatostatin is also down-regulated in major depressive disorder, and more robustly so in women with depression, hence mirroring the increased female prevalence of the disorder. This proposal follows up on recent findings from the candidate, Dr. Marianne Seney, indicating a role for XY genetic sex in regulating anxiety-like behaviors and expression of somatostatin, and of an opposing effect of adult testosterone on the behavioral effects of XY genetic sex. These translational mouse studies are directly informed by human postmortem findings and will specifically investigate (i) the "opposing" effect of XY genetic sex and adult circulating testosterone on anxiety-like behavior and on molecular correlates, and (ii) whether manipulating the function of inhibitory neurons that express somatostatin will affect the balance between genetic sex and circulating testosterone in adult behavioral outcomes. The candidate, Dr. Marianne Seney, is the ideal individual to perform the proposed research, based on her previous research experience in the fields of neuroendocrinology and of sexual dimorphism in the rodent brain. The mentor, Dr. Etienne Sibille, will provide expertise in the translational approach to study causality of altered biological pathways or cellular mechanisms involved in the pathophysiology of depression, together offering a unique and synergistic environment in which to study sex differences in depression and anxiety. The co-mentor, Dr. Colleen McClung, will provide essential training in rodent pharmacogenetic techniques to modulate function of specific cell populations in the brain. Co-mentor, Dr. George Tseng, will provide critical support in using state of the art bioinformatics and statistical approaches to interpret large behavioral and molecular datasets. To perform the proposed research and interpret results, Dr. Seney will benefit from a group of internal and external expert consultants, and will obtain additional training in proteomics and in exposure to clinical realities of mood and anxiety disorders. The Department of Psychiatry at the University of Pittsburgh offers a well-funded environment with a nationally and internationally recognized reputation as a premier research institution, making it the ideal location for Dr. Seney to perform her research and gain essential training. At completion of this proposal, Dr. Seney will be poised to lead her own research program aimed at using translational approaches to understand sex differences in mood and anxiety disorders.

描述（由申请人提供）：生长抑素，一种在大脑中抑制性神经元子集中表达的神经肽，在人类的多种脑疾病中，包括精神分裂症，双极抑郁症和阿尔茨海默氏病。生长抑素在重度抑郁症中也被下调，并且在抑郁症的女性中更加坚固，因此反映了女性患病率的增加。该提案遵循候选人玛丽安·塞尼（Marianne Seney）博士的最新发现，表明XY遗传性别在调节焦虑症行为和生长抑素的表达以及成人睾丸激素对XY遗传性别的行为影响方面的作用。这些翻译小鼠的研究直接通过人类验尸发现来告知（i）（i）XY遗传性别和成人循环睾丸激素对焦虑症行为和分子相关的“相反”影响，以及（ii）操纵表达大麻素的抑制性神经元的功能是否会影响遗传性测试的抑制作用，这会影响遗传性测试彼此的表现。候选人玛丽安·塞尼（Marianne Seney）博士是根据她以前在神经内分泌学领域和啮齿动物大脑中的性二态性领域进行的研究经验，是进行拟议研究的理想个体。导师Etienne Sibille博士将在研究改变的因果关系方面提供专业知识 抑郁症的病理生理学涉及的生物途径或细胞机制，共同提供独特而协同的环境，在其中研究抑郁症和焦虑症中的性别差异。院长Colleen McClung博士将提供啮​​齿动物药物遗传学技术的基本培训，以调节大脑特定细胞群体的功能。乔治·滕（George Tseng）博士将在使用最先进的生物信息学和统计方法来解释大型行为和分子数据集方面提供重要的支持。为了执行拟议的研究和解释结果，塞尼博士将从一组内部和外部专家顾问中受益，并将获得有关蛋白质组学以及对情绪和焦虑症的临床现实的额外培训。匹兹堡大学精神病学系提供了一个充分资金的环境，并在国际和国际公认的主要研究机构享有声誉，这使其成为塞内尼博士进行研究并获得基本培训的理想场所。完成此提案后，塞尼博士将有望领导自己的研究计划，旨在使用翻译方法来了解情绪和焦虑症的性别差异。