A Role for the Orphan Receptor, GPR37, in Estradiol-induced Changes in Sleep-Wake States
孤儿受体 GPR37 在雌二醇诱导的睡眠-觉醒状态变化中的作用
基本信息
- 批准号:10677913
- 负责人:
- 金额:$ 4.02万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-08-30 至 2026-08-29
- 项目状态:未结题
- 来源:
- 关键词:ADORA2A geneAdenosineAdultAffectAgonistAnimalsAttenuatedBrainBrain StemCell NucleusCellsCo-ImmunoprecipitationsCorpus striatum structureCoupledCuriositiesDiagnosisEquilibriumEstradiolEstrogen ReceptorsEstrogensFemaleG-Protein-Coupled ReceptorsGPR37 receptorGonadal Steroid HormonesHormonalHypothalamic structureInfusion proceduresLateralLinkMeasuresMediatingMenopauseMessenger RNAModelingNeuromodulatorNeuronsOrphanPlayPopulationPregnancyProteinsRat TransgeneRattusReceptor SignalingReportingRoleSleepSleep DisordersSleep Wake CycleSleep disturbancesSleeplessnessSurfaceTechniquesTestingUp-RegulationViralViral VectorWakefulnessWomanexperimental studyextracellularfallsinnovationinsightmRNA Expressionmennon rapid eye movementpharmacologicpreoptic nucleuspressureprotein expressionreceptorreceptor couplingsleep difficulty
项目摘要
Project Summary
Studies have shown that women report more sleep difficulties and are more likely to be diagnosed with insomnia
compared to men. Sleep disturbances are more likely to occur in women during times of hormonal fluctuations,
including pregnancy and menopause, thus indicating that sex hormones play a role in the sleep-wake cycle.
Understanding more about how sex hormones act to influence sleep can help us develop targeted treatments
for women who suffer from sleep disorders. There are 2 major sleep centers in the brain, both located in the
hypothalamus – the median preoptic nucleus (MnPO) and the ventrolateral preoptic nucleus (VLPO). There are
estrogen receptors located in the MnPO, but not in the VLPO, suggesting that estrogen acts via the MnPO to
regulate sleep-wake states. The MnPO is thought to promote sleep by inhibiting wake-promoting neurons in the
brain. It has been found that estradiol (E2) infusion into the MnPO increases wake and decreases sleep in
ovariectomized female rats, however the mechanism by which sleep is disrupted by E2 is largely unknown.
During wakefulness, adenosine accumulates in the brain and increases sleep pressure, causing tiredness. The
A1 and A2A receptors (A1R and A2AR) are expressed in the MnPO and play an important role in regulating the
effects of adenosine in the brain. Infusion of an A1R agonist into the MnPO has been found to increase wake
and decrease sleep in rats, while infusion of an A2AR agonist has been found to increase sleep and decrease
wake. E2 has been hypothesized to influence the inhibitory/excitatory adenosinergic balance in the MnPO, as,
in the presence of E2, the sleep-promoting effects of an A2AR agonist are blocked. One potential target of E2 is
G protein-coupled receptor 37 (GPR37), as it has been shown to inhibit A2AR surface expression and function in
the striatum. This project will test the hypothesis that E2 is decreasing NREM sleep and increasing wake
by attenuating A2AR signaling through GPR37 modulation. To examine the effects of GPR37 in the MnPO,
we are going to (1) Determine if E2 is sufficient for GPR37 upregulation in the MnPO, (2) Determine if A2AR and
GPR37 form an interaction in the sleep active cells of the MnPO, and (3) Determine if GPR37 is necessary to
cause E2-induced changes in sleep-wake states. Understanding estradiol’s role in the disruption of the sleep-
wake cycle will help us gain greater insight into one of the unique mechanisms of insomnia in women and
ultimately with how we can better treat insomnia in a substantial portion of the population.
项目总结
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 }}
Katie Kruk其他文献
Katie Kruk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 }}
相似国自然基金
基于ADK/Adenosine调控DNA甲基化探讨“利湿化瘀通络”法对2型糖尿病肾病足细胞裂孔膜损伤的干预机制研究
- 批准号:82074359
- 批准年份:2020
- 资助金额:55 万元
- 项目类别:面上项目
细胞外腺苷(Adenosine)作为干细胞旁分泌因子的生物学鉴定和功能分析
- 批准号:81570244
- 批准年份:2015
- 资助金额:57.0 万元
- 项目类别:面上项目
Adenosine诱导A1/A2AR稳态失衡启动慢性低灌注白质炎性损伤及其机制
- 批准号:81171113
- 批准年份:2011
- 资助金额:55.0 万元
- 项目类别:面上项目
相似海外基金
Targeting the A2B Adenosine Receptor for Immunoprevention of Pancreatic Cancer
靶向 A2B 腺苷受体用于胰腺癌的免疫预防
- 批准号:
10929664 - 财政年份:2023
- 资助金额:
$ 4.02万 - 项目类别:
Exploring the role of adenosine A2A receptors in Schizophrenia using opto-pharmacologically controlled allosteric modulation.
利用光药理学控制的变构调节探索腺苷 A2A 受体在精神分裂症中的作用。
- 批准号:
23K14685 - 财政年份:2023
- 资助金额:
$ 4.02万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
The Role of Adenosine Kinase in Mixed Diastolic Heart Failure and Alzheimer Disease
腺苷激酶在混合性舒张性心力衰竭和阿尔茨海默病中的作用
- 批准号:
10679989 - 财政年份:2023
- 资助金额:
$ 4.02万 - 项目类别:
Allostery-driven G protein selectivity in the adenosine A1 receptor
腺苷 A1 受体中变构驱动的 G 蛋白选择性
- 批准号:
BB/W016974/1 - 财政年份:2023
- 资助金额:
$ 4.02万 - 项目类别:
Research Grant
Investigation of new test methods for adenosine-sensitive atrioventricular block
腺苷敏感型房室传导阻滞新检测方法的探讨
- 批准号:
23K07566 - 财政年份:2023
- 资助金额:
$ 4.02万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Probing the role of adenosine pathway in SIV pathogenesis
探讨腺苷途径在 SIV 发病机制中的作用
- 批准号:
10760676 - 财政年份:2023
- 资助金额:
$ 4.02万 - 项目类别:
The role of A1 adenosine receptor signaling in the decline of S. pneumoniae killing by neutrophils in vaccinated aged hosts
A1 腺苷受体信号传导在疫苗接种老年宿主中中性粒细胞杀伤肺炎链球菌下降中的作用
- 批准号:
10605737 - 财政年份:2023
- 资助金额:
$ 4.02万 - 项目类别:
Adenosine triphosphate as a master variable for biomass in the oceanographic context
三磷酸腺苷作为海洋学背景下生物量的主变量
- 批准号:
2319114 - 财政年份:2023
- 资助金额:
$ 4.02万 - 项目类别:
Standard Grant
The Biology of Microglia: Adenosine A3 Receptor Suppression
小胶质细胞的生物学:腺苷 A3 受体抑制
- 批准号:
RGPIN-2019-06289 - 财政年份:2022
- 资助金额:
$ 4.02万 - 项目类别:
Discovery Grants Program - Individual
Postnatal development of adenosine kinase in the brainstem network that controls breathing
控制呼吸的脑干网络中腺苷激酶的出生后发育
- 批准号:
573323-2022 - 财政年份:2022
- 资助金额:
$ 4.02万 - 项目类别:
University Undergraduate Student Research Awards