Relaxin 3 and sex differences in post-stroke depression

松弛素 3 与中风后抑郁症的性别差异

• 批准号: 9453969
• 负责人: ELIZABETH M BYRNES
• 金额: $ 24.75万
• 依托单位: TUFTS UNIVERSITY BOSTON
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-30 至 2019-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9453969
• 关键词: Adrenal Glands; Affect; Affective; Amygdaloid structure; Anhedonia; Animal Model; Animals; Anti-Anxiety Agents; Behavior; Brain region; Cause of Death; Circadian Rhythms; Clinical; Comorbidity; Corticotropin-Releasing Hormone; Data; Development; Endothelin-1; Epidemiology; Exploratory/Developmental Grant; Family; Female; Functional disorder; Genetic Transcription; Goals; High Prevalence; Hormones; Hyperactive behavior; Hypothalamic structure; Incentives; Incidence; Infarction; Injury; Ischemia; Ischemic Stroke; Knockout Mice; Language Disorders; Lesion; Life; Measures; Mental Depression; Modeling; Modification; Monitor; Mood Disorders; Motivation; Neurological outcome; Neuropeptides; Outcome; Patients; Peptides; Phase; Pituitary Gland; Population; Pre-Clinical Model; Prefrontal Cortex; Prevalence; Property; Rattus; Receptor Activation; Rehabilitation therapy; Relaxin; Reporting; Rewards; Role; Self Administration; Severities; Sex Characteristics; Stress; Stroke; Sucrose; Swimming; Symptoms; System; Testing; Time; United States; Vasoconstrictor Agents; Woman; Work; acute stroke; base; common symptom; depressive symptoms; disability; experience; functional outcomes; hypothalamic-pituitary-adrenal axis; male; men; middle cerebral artery; motivated behavior; neuromechanism; new therapeutic target; novel; novel therapeutics; post stroke; post stroke depression; pre-clinical; preclinical study; preference; receptor; receptor expression; sex; stroke treatment

Every year in the United States over 600,000 people experience their first stroke. Indeed, stroke is the 4th leading cause of death in the U.S. and one of the leading causes of long-term disability. There are significant sex differences in the epidemiology of stroke as well as the neurological and functional outcomes following stroke. Overall, men have a higher prevalence of stroke while women have poorer outcomes. One consequence that is reported in both men and women is the onset of post-stroke depression, although it is more common in women. Post- stroke depression is associated with significant long-term disability and often interferes with rehabilitation efforts. In spite of the pervasiveness of post-stroke depression and the negative impact of depression on long-term outcomes, few animal models have investigated the development of depressive-like behaviors post stroke. Relaxin 3 is a highly conserved neuropeptide that modulates a number of behaviors with data suggesting both anxiolytic and anti-depressant properties. Importantly, the relaxin 3 system demonstrates significant sex differences. The purpose of the current proposal is to examine the development of post-stroke depression using well-validated measures of anhedonia and effort-based responding in male and female rats (Specific Aim 1). In addition, these studies will also examine the sex-specific effects of ischemic stroke on the relaxin 3 system and will investigate the efficacy of relaxin 3 as a novel therapeutic in post-stroke depression (Specific Aim 2). Together, these studies will determine sex-specific effects of stroke-induced changes in affective behaviors with an emphasis on incentive motivation and the potential role of the neuropeptide relaxin 3 in the expression of depressive-like behaviors.

在美国，每年有超过60万人经历他们的第一次中风。事实上，中风 是美国第四大死亡原因，也是长期死亡的主要原因之一。 残疾。在中风的流行病学以及 脑卒中后的神经和功能结局。总体而言，男性的患病率较高， 而女性的结果更差。据报道，在男性和女性中， 女性是中风后抑郁症的发病原因，尽管它在女性中更常见。后 中风抑郁症与严重的长期残疾有关， 康复工作。尽管中风后抑郁症和消极情绪普遍存在， 抑郁症对长期结果的影响，很少有动物模型研究了抑郁症的影响。 中风后抑郁样行为的发展。松弛素3是一种高度保守的 一种神经肽，它调节许多行为，数据表明它既有抗焦虑作用， 抗氧化性能。重要的是，松弛素3系统表现出显著的性别差异， 差异目前的建议的目的是检查中风后的发展， 抑郁症使用有效的措施，快感缺乏和努力为基础的反应，在男性 和雌性大鼠（具体目标1）。此外，这些研究还将检查性别特异性 缺血性中风对松弛素3系统的影响，并将研究松弛素3作为 中风后抑郁症的一种新疗法（具体目标2）。这些研究将 确定中风引起的情感行为变化的性别特异性影响， 强调激励动机和神经肽松弛素3在神经系统中的潜在作用， 抑郁样行为的表现。