Wyoming Sensory Biology COBRE

怀俄明州感官生物学 COBRE

基本信息

  • 批准号:
    10395258
  • 负责人:
  • 金额:
    $ 28.74万
  • 依托单位:
  • 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:
    2017-09-01 至 2023-07-31
  • 项目状态:
    已结题

项目摘要

Abstract Women are much more likely than men to develop Alzheimer’s disease (AD) and related dementias, which are associated with progressive disruption of circadian rhythms. Additionally, women are more likely than men to develop circadian disorders, such as sleep disorders, and one particular feature of circadian dysfunction in patients with AD and related dementias is “sundowning syndrome”, a poorly understood clinical phenomenon characterized by agitation, aggression, and delirium during the early evening hours. Sundowing symptoms have a major impact on the quality of life for both the patient and their caregivers, who are also more likely to be women, and often lead to the decision to seek institutionalization. The neurobiology of sundowning remains unknown, however the temporal periodicity of sundowning symptoms suggests a possible disturbance in the master circadian clock, the suprachiasmatic nucleus (SCN) of the hypothalamus, or in the pathways by which the SCN modulates particular rhythms. Rhythms of sleep-wake and locomotor activity (LMA) are regulated by the SCN via a pathway through its major postsynaptic target, the subparaventricular zone (SPZ), to the dorsomedial hypothalamus (DMH). Additionally, we recently demonstrated that the propensity for behavioral aggression also follows a daily rhythm that is regulated by the SCN, via an additional pathway through the SPZ, to the ventromedial hypothalamus (VMH). Importantly, disrupting this SCNSPZVMH pathway led to increased aggression during the early resting phase (the light period for nocturnal mice), which is temporally analogous to when AD and dementia patients who experience sundowning display increased agitation and aggression. This suggests that the function of certain structures within this circuit may be compromised in AD and dementia. Interesting, women have also been shown to have a particular profile of inflammatory markers in AD, however these differences have never been examined directly in areas associated with circadian regulation. We have begun examining circadian rhythms in the TAPP mouse model, which develops amyloid-beta (a-beta) plaques and tau neurofibrillary tangles (both hallmarks of AD neuropathology), and our preliminary results suggest that these mice exhibit increased early resting period aggression and disrupted LMA at very early ages of AD pathology. In this proposal, we will examine whether sex-differences in specific inflammatory markers are associated with sex differences in increased aggression during the early resting phase and disrupted LMA rhythms in female and male TAPP mice, and in their female and male wild-type controls. We will focus our analysis in a circuit-based and region-specific manner, by specifically examining lysates from dissected hypothalamic tissue containing the SCN and SPZ, and dissected midbrain tissue containing areas which we know project to the circadian system and which display heavy phosphorylated tau pathology at later ages.
抽象的 女性比男性更有可能发展阿尔茨海默氏病(AD)和相关痴呆症,这是 与昼夜节律的进行性破坏有关。此外,女人比男人更有可能 患有昼夜节律疾病,例如睡眠障碍,以及昼夜节律功能障碍的一个特殊特征 AD和相关痴呆症患者是“日落综合征”,这是一种熟悉的临床现象 傍晚时分以搅动,侵略和del妄为特征。杂音符号有 对患者及其护理人员的生活质量的重大影响,他们也更有可能是 妇女,并且经常导致寻求制度化的决定。日落的神经生物学仍然存在 未知,但是日落症状的暂时周期性表明 昼夜节律大师时钟,下丘脑的上核(SCN)或在其途径中 SCN调节特定的节奏。睡眠觉醒和运动活动(LMA)的节奏受到调节 通过其主要突触后靶标的途径(SPZ)的SCN到达 背侧下丘脑(DMH)。此外,我们最近证明了行为的希望 侵略性还遵循由SCN调节的每日节奏,通过SPZ的额外途径, 到腹侧下丘脑(VMH)。重要的是,破坏此SCNSPZVMH途径导致 在早期休息阶段(夜间小鼠的光周期)提高了侵略性,这是暂时的 类似于何时经历阳光表现出的AD和痴呆症患者的搅动增加和 侵略。这表明该电路中某些结构的功能可能会在AD中损害 和痴呆症。有趣的是,妇女还显示出具有特殊的炎症标志物的特征 但是,AD,这些差异从未在与昼夜节律有关的领域进行直接检查。 我们已经开始研究Tapp小鼠模型中的昼夜节律,该模型发展了淀粉样蛋白β(A-Beta) 斑块和tau神经原纤维缠结(AD神经病理学的标志)和我们的初步结果 表明这些小鼠暴露于早期的早期LMA的早期休息时间增加了 广告病理学。在此提案中,我们将研究特定炎症标记中的性别差异是否是 与早期休息阶段侵略性增加的性别差异相关,而LMA中断 女性和雄性Tapp小鼠的节奏以及其女性和男性野生型对照。我们将集中精力 以基于电路和区域特异性的方式分析,通过专门检查解剖的裂解物 含有SCN和SPZ的下丘脑组织,并解剖包含我们的中脑组织 了解昼夜节律系统的项目,并在后来显示出大量的磷酸化tau病理学。

项目成果

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Qian-Quan Sun其他文献

Qian-Quan Sun的其他文献

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{{ truncateString('Qian-Quan Sun', 18)}}的其他基金

A Long-range Recurrent Neural Network Mediates Threat Induced Innate Sensorimotor Integrations
远程循环神经网络介导威胁诱发的先天感觉运动整合
  • 批准号:
    10539071
  • 财政年份:
    2022
  • 资助金额:
    $ 28.74万
  • 项目类别:
A Long-range Recurrent Neural Network Mediates Threat Induced Innate Sensorimotor Integrations
远程循环神经网络介导威胁诱发的先天感觉运动整合
  • 批准号:
    10626968
  • 财政年份:
    2022
  • 资助金额:
    $ 28.74万
  • 项目类别:
Core A: Administrative Core
核心A:行政核心
  • 批准号:
    10216276
  • 财政年份:
    2017
  • 资助金额:
    $ 28.74万
  • 项目类别:
Wyoming Sensory Biology COBRE
怀俄明州感官生物学 COBRE
  • 批准号:
    10398656
  • 财政年份:
    2017
  • 资助金额:
    $ 28.74万
  • 项目类别:
Wyoming Sensory Biology COBRE
怀俄明州感官生物学 COBRE
  • 批准号:
    10372244
  • 财政年份:
    2017
  • 资助金额:
    $ 28.74万
  • 项目类别:
Wyoming Sensory Biology COBRE
怀俄明州感官生物学 COBRE
  • 批准号:
    10871969
  • 财政年份:
    2017
  • 资助金额:
    $ 28.74万
  • 项目类别:
Wyoming Sensory Biology COBRE
怀俄明州感官生物学 COBRE
  • 批准号:
    10714606
  • 财政年份:
    2017
  • 资助金额:
    $ 28.74万
  • 项目类别:
Wyoming Sensory Biology COBRE
怀俄明州感官生物学 COBRE
  • 批准号:
    10216275
  • 财政年份:
    2017
  • 资助金额:
    $ 28.74万
  • 项目类别:
Administrative Core
行政核心
  • 批准号:
    10923745
  • 财政年份:
    2017
  • 资助金额:
    $ 28.74万
  • 项目类别:
Wyoming Sensory Biology COBRE
怀俄明州感官生物学 COBRE
  • 批准号:
    10798707
  • 财政年份:
    2017
  • 资助金额:
    $ 28.74万
  • 项目类别:

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晚年的家庭照顾者:对患有自闭症和发育障碍的成年人的家庭福祉和心理健康的纵向研究
  • 批准号:
    10588105
  • 财政年份:
    2023
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  • 批准号:
    10661910
  • 财政年份:
    2023
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    $ 28.74万
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5-HT 2C Receptor and Alzheimer's Disease
5-HT 2C 受体与阿尔茨海默病
  • 批准号:
    10732703
  • 财政年份:
    2023
  • 资助金额:
    $ 28.74万
  • 项目类别:
Germline Determinants of Prostate Cancer Evolution
前列腺癌进化的种系决定因素
  • 批准号:
    10587968
  • 财政年份:
    2023
  • 资助金额:
    $ 28.74万
  • 项目类别:
Mental Health in Autistic Adults: An RDoC Approach
成人自闭症患者的心理健康:RDoC 方法
  • 批准号:
    10698071
  • 财政年份:
    2022
  • 资助金额:
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