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.

每年在美国，有超过60万人的首次中风。确实，中风是美国第四大死亡原因，也是长期的主要原因之一残疾。中风的流行病学以及中风后神经和功能结果。总体而言，男人的患病率更高中风，而女性的结果较差。两名男子和妇女是势后抑郁症的开始，尽管在女性中更常见。邮政- 中风抑郁症与重大的长期残疾有关，并且经常干扰康复工作。尽管势后抑郁症和负面抑郁症对长期结局的影响，很少有动物模型研究了中风后类似抑郁症行为的发展。放松蛋白3是高度保守的神经肽可以调节许多行为，并提示抗焦虑和抗抑郁剂特性。重要的是，放松素3系统表现出重要的性爱差异。当前建议的目的是检查中风后的发展抑郁症使用雄性的Anhedonia和基于努力的反应进行验证的措施和雌性大鼠（特定目标1）。此外，这些研究还将检查特定的性别缺血性卒中对松弛素3系统的影响，并将研究松弛素3的功效中风后抑郁症的一种新型治疗方法（特定目标2）。这些研究将在一起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在表达抑郁症状行为。