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

基本信息

批准号：
9568818
负责人：
ELIZABETH M BYRNES
金额：
$ 20.63万
依托单位：
TUFTS UNIVERSITY BOSTON
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-09-30 至 2020-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9568818
关键词：
Adrenal Glands Affect Affective Amygdaloid structure Anhedonia Animal Model Animals Anti-Anxiety Agents Antidepressive 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 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 model stroke patient

项目摘要

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 600,000 人经历第一次中风。确实，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。脑卒中的流行病学以及发病率存在显着的性别差异中风后的神经和功能结果。总体而言，男性患病率较高中风，而女性的预后较差。在男性和女性中均报告了一种后果女性是中风后抑郁症的发病者，尽管它在女性中更为常见。邮政- 中风抑郁症与严重的长期残疾有关，并且经常干扰康复工作。尽管中风后抑郁症普遍存在，并且负面影响抑郁症对长期结果的影响，很少有动物模型研究过中风后抑郁样行为的发展。松弛素 3 是一种高度保守的调节多种行为的神经肽，数据表明具有抗焦虑和抗焦虑作用抗抑郁特性。重要的是，松弛素 3 系统表现出显着的性别差异差异。当前提案的目的是检查中风后的发展使用经过充分验证的男性快感缺乏和基于努力的反应措施来治疗抑郁症和雌性大鼠（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 的功效一种治疗中风后抑郁症的新疗法（具体目标 2）。这些研究共同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 在抑郁样行为的表达。