Comorbid mood and urogenital disorders in mice following neonatal maternal separation

新生儿母亲分离后小鼠的共病情绪和泌尿生殖系统疾病

基本信息

项目摘要

DESCRIPTION (provided by applicant): An estimated 11% of women and 5% of men suffer from symptoms related to interstitial cystitis/painful bladder syndrome (IC/PBS), which generates a minimum $20 billion in direct medical costs annually in the United States. Approximately 17-40% of IC/PBS patients exhibit symptoms of a secondary chronic pelvic pain disorder and up to half suffer from depression and/or panic disorder. Comorbidity of syndromes has been associated with altered functioning of the hypothalamic-pituitary-adrenal (HPA) axis, which regulates stress response and influences the perception of pain. Corticotropin-releasing factor (CRF) is the principal initiator of the stress response and, along with the related urocortis (Ucn), mediates downstream stress responses, as well as influences both positive and negative feedback onto the HPA axis. CRF is also a potent stimulator of peripheral mast cell degranulation and functions as a neuropeptide involved in regulating the central micturition reflex. Early life stress or trauma is a significant risk factor for HPA axis disruption and significantly increases the likelihood of developing chronic pelvic pain and mood disorders during adolescence or adulthood. Rodent models of neonatal stress display disruption of proper feedback onto the HPA axis, resulting in anhedonia, anxiety-like behaviors, and hyperalgesia and neurogenic inflammation in the pelvic viscera. Voluntary exercise has been shown to reverse many abnormalities associated with early life stress, including symptoms associated with chronic pain and mood disorders. The goal of the current proposal is to understand how manipulation of the limbic regulation and downstream output of the HPA axis affects both behavior and urogenital sensitivity in mice that were exposed to early life stress. Our central hypothesis is that comorbid urogenital pain syndromes and mood disorders in NMS mice arise from increased output of the HPA axis, due to diminished negative regulatory input from the hippocampus, and can be differentially attenuated by peripherally- and centrally-mediated interventions. We have designed three specific aims (SAs) to test this hypothesis. SA1 will determine how NMS alters the expression patterns and downstream peripheral influences of CRF-responsive brain regions. SA2 will determine the impact of mast cell activation on urogenital sensitivity and micturition in NMS mice. SA3 will determine the impact of voluntary exercise on improving hippocampal regulatory input onto the HPA axis in NMS mice. At the completion of this project, we will have gained novel insight on the mechanisms underlying comorbid pelvic pain and mood disorders following early life stress. We will also have obtained preclinical evidence on the efficacy of exercise, an easily translatable intervention, as a potentil treatment strategy for these debilitating disorders.
描述(由申请人提供):估计有11%的女性和5%的男性患有与间质性膀胱炎/膀胱疼痛综合征(IC/PBS)相关的症状,在美国每年产生至少200亿美元的直接医疗费用。大约17-40%的IC/PBS患者表现出继发性慢性盆腔疼痛障碍的症状,多达一半的患者患有抑郁症和/或惊恐障碍。综合征的合并症与下丘脑-垂体-肾上腺(HPA)轴功能的改变有关,HPA轴调节应激反应并影响疼痛感知。促肾上腺皮质激素释放因子(CRF)是应激反应的主要起始因子,并且沿着相关的urocortis(Ucn)介导下游应激反应,以及影响到HPA轴的正反馈和负反馈。CRF也是外周肥大细胞脱颗粒的有效刺激物,并作为神经肽参与调节中枢排尿反射。早期生活压力或创伤是HPA轴破坏的重要风险因素,并显着增加青春期或成年期发生慢性盆腔疼痛和情绪障碍的可能性。新生儿应激的啮齿动物模型显示对HPA轴的适当反馈中断,导致快感缺乏、焦虑样行为、痛觉过敏和盆腔脏器中的神经源性炎症。自愿运动已被证明可以逆转许多与早期生活压力相关的异常,包括与慢性疼痛和情绪障碍相关的症状。当前提案的目标是了解如何操纵边缘系统调节和HPA轴的下游输出影响暴露于早期生活压力的小鼠的行为和泌尿生殖敏感性。我们的中心假设是,合并泌尿生殖系统疼痛综合征和情绪障碍的NMS小鼠产生的HPA轴的输出增加,由于减少负调控输入从海马,并可以通过外周和中枢介导的干预差异衰减。我们设计了三个具体的目标(SA)来验证这一假设。SA 1将决定NMS如何改变CRF反应脑区的表达模式和下游外周影响。SA 2将确定肥大细胞活化对NMS小鼠泌尿生殖敏感性和排尿的影响。SA 3将确定自主运动对改善NMS小鼠中海马对HPA轴的调节输入的影响。在这个项目完成后,我们将获得新的见解的机制,共病盆腔疼痛和情绪障碍后,早期生活压力。我们还将获得有关运动功效的临床前证据,运动是一种易于转化的干预措施,是这些使人衰弱的疾病的潜在治疗策略。

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

Julie A Carlsten Christianson其他文献

Julie A Carlsten Christianson的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('Julie A Carlsten Christianson', 18)}}的其他基金

Effect of neonatal and adult stress on pelvic pain disorders and comorbidity
新生儿和成人压力对盆腔疼痛疾病和合并症的影响
  • 批准号:
    9267976
  • 财政年份:
    2014
  • 资助金额:
    $ 33.98万
  • 项目类别:
Effect of neonatal and adult stress on pelvic pain disorders and comorbidity
新生儿和成人压力对盆腔疼痛疾病和合并症的影响
  • 批准号:
    10374858
  • 财政年份:
    2014
  • 资助金额:
    $ 33.98万
  • 项目类别:
Effect of neonatal and adult stress on pelvic pain disorders and comorbidity
新生儿和成人压力对盆腔疼痛疾病和合并症的影响
  • 批准号:
    9467483
  • 财政年份:
    2014
  • 资助金额:
    $ 33.98万
  • 项目类别:
Comorbid mood and urogenital disorders in mice following neonatal maternal separation
新生儿母亲分离后小鼠的共病情绪和泌尿生殖系统疾病
  • 批准号:
    9318526
  • 财政年份:
    2014
  • 资助金额:
    $ 33.98万
  • 项目类别:
Effect of neonatal and adult stress on pelvic pain disorders and comorbidity
新生儿和成人压力对盆腔疼痛疾病和合并症的影响
  • 批准号:
    10612841
  • 财政年份:
    2014
  • 资助金额:
    $ 33.98万
  • 项目类别:
Comorbid mood and urogenital disorders in mice following neonatal maternal separation
新生儿母亲分离后小鼠的共病情绪和泌尿生殖系统疾病
  • 批准号:
    9118993
  • 财政年份:
    2014
  • 资助金额:
    $ 33.98万
  • 项目类别:
Comorbid mood and urogenital disorders in mice following neonatal maternal separation
新生儿母亲分离后小鼠的共病情绪和泌尿生殖系统疾病
  • 批准号:
    8802966
  • 财政年份:
    2014
  • 资助金额:
    $ 33.98万
  • 项目类别:
Effect of neonatal and adult stress on pelvic pain disorders and comorbidity
新生儿和成人压力对盆腔疼痛疾病和合并症的影响
  • 批准号:
    8916710
  • 财政年份:
    2014
  • 资助金额:
    $ 33.98万
  • 项目类别:
Effect of neonatal and adult stress on pelvic pain disorders and comorbidity
新生儿和成人压力对盆腔疼痛疾病和合并症的影响
  • 批准号:
    8698099
  • 财政年份:
    2014
  • 资助金额:
    $ 33.98万
  • 项目类别:
IMPACT OF EARLY EXPERIENCE ON VULVOVAGINAL SENSITIVITY IN ADULT MOUSE
早期经验对成年小鼠外阴阴道敏感性的影响
  • 批准号:
    8360687
  • 财政年份:
    2011
  • 资助金额:
    $ 33.98万
  • 项目类别:

相似海外基金

Cognitive and non-cognitive abilities and career development during adolescence and adult development: from the perspective of genetic and environmental structure
青春期和成人发展期间的认知和非认知能力与职业发展:从遗传和环境结构的角度
  • 批准号:
    23K02900
  • 财政年份:
    2023
  • 资助金额:
    $ 33.98万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
ADOLESCENCE: A SENSITIVE PERIOD FOR SHAPING THE ADULT SOCIAL BRAIN
青春期:塑造成人社交大脑的敏感时期
  • 批准号:
    RGPIN-2022-05266
  • 财政年份:
    2022
  • 资助金额:
    $ 33.98万
  • 项目类别:
    Discovery Grants Program - Individual
Joint contributions of affiliative social contact, stress in adolescence and oxytocin to fear behaviour in adult rats
亲和性社会接触、青春期压力和催产素对成年大鼠恐惧行为的共同作用
  • 批准号:
    RGPIN-2019-04790
  • 财政年份:
    2022
  • 资助金额:
    $ 33.98万
  • 项目类别:
    Discovery Grants Program - Individual
Joint contributions of affiliative social contact, stress in adolescence and oxytocin to fear behaviour in adult rats
亲和性社会接触、青春期压力和催产素对成年大鼠恐惧行为的共同作用
  • 批准号:
    RGPIN-2019-04790
  • 财政年份:
    2021
  • 资助金额:
    $ 33.98万
  • 项目类别:
    Discovery Grants Program - Individual
ADOLESCENCE: A SENSITIVE PERIOD FOR SHAPING THE ADULT SOCIAL BRAIN
青春期:塑造成人社交大脑的敏感时期
  • 批准号:
    RGPIN-2016-03714
  • 财政年份:
    2021
  • 资助金额:
    $ 33.98万
  • 项目类别:
    Discovery Grants Program - Individual
Impact on adult mouse brain of oral THC and CBD consumption during adolescence
青春期口服 THC 和 CBD 对成年小鼠大脑的影响
  • 批准号:
    10206087
  • 财政年份:
    2020
  • 资助金额:
    $ 33.98万
  • 项目类别:
Joint contributions of affiliative social contact, stress in adolescence and oxytocin to fear behaviour in adult rats
亲和性社会接触、青春期压力和催产素对成年大鼠恐惧行为的共同作用
  • 批准号:
    RGPIN-2019-04790
  • 财政年份:
    2020
  • 资助金额:
    $ 33.98万
  • 项目类别:
    Discovery Grants Program - Individual
Investigating the Social Determinant and Developmental Risk Patterns in Childhood and Adolescence Associated with Adult Asthma and Diabetes Onset
调查儿童期和青少年期与成人哮喘和糖尿病发病相关的社会决定因素和发育风险模式
  • 批准号:
    450250
  • 财政年份:
    2020
  • 资助金额:
    $ 33.98万
  • 项目类别:
    Studentship Programs
ADOLESCENCE: A SENSITIVE PERIOD FOR SHAPING THE ADULT SOCIAL BRAIN
青春期:塑造成人社交大脑的敏感时期
  • 批准号:
    RGPIN-2016-03714
  • 财政年份:
    2020
  • 资助金额:
    $ 33.98万
  • 项目类别:
    Discovery Grants Program - Individual
Impact on adult mouse brain of oral THC and CBD consumption during adolescence
青春期口服 THC 和 CBD 对成年小鼠大脑的影响
  • 批准号:
    10039866
  • 财政年份:
    2020
  • 资助金额:
    $ 33.98万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了