Centrifugal regulation of olfactory function by melanin-concentrating hormone
黑色素浓缩激素对嗅觉功能的离心调节
基本信息
- 批准号:10610404
- 负责人:
- 金额:$ 31.68万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-04-01 至 2026-03-31
- 项目状态:未结题
- 来源:
- 关键词:AblationAcuteAddressAffectAnimalsAnteriorAreaAxonBehaviorBehavioralBiochemicalBiological AssayBrainBrain regionCellsCentral Nervous SystemChemicalsCiliaDetectionDiscriminationEatingEnvironmentExcisionFeeding behaviorsFoodFood deprivation (experimental)Functional disorderFutureGene ExpressionGenesGeneticGoalsGrantHealthHumanHungerHypothalamic structureImageImmediate-Early GenesInterneuronsLateralMCHR1 geneMapsMediatingModelingMolecularMonitorMusMutant Strains MiceNasal cavityNeuronsNeuropeptidesNeurophysiology - biologic functionObesityOdorsOlfactory EpitheliumOlfactory PathwaysOlfactory tubercleOrganellesOrganismPathway interactionsPatientsPeptidesPhenotypePhysiologicalPlayPopulationProcessQuality of lifeREM SleepRegulationResearchRoleSatiationSensorySignal PathwaySignal TransductionSiteSleepSleep DeprivationSmell PerceptionTechniquesTestingViralVolatilizationWakefulnessWestern BlottingWhole Body Plethysmographybehavior testbehavioral outcomebehavioral responsecellular targetingciliopathycircadiandesignexperimental studyfeedingfood restrictiongenetic manipulationglutamatergic signalinghabituationhormonal signalsinsightmelanin-concentrating hormonemelanin-concentrating hormone receptormitral cellmouse modelmutantneuroregulationolfactory bulbolfactory nucleiolfactory sensory neuronsopen field behaviorpharmacologicpiriform cortexreceptorresponsesensory mechanismsensory systemsleep patterntransmission process
项目摘要
Project Summary
The sense of smell is essential for maintaining full human health and quality of life. It plays an
important role in the detection of environmental dangers as well guiding decisions such as what
foods to eat. However, olfactory processing is influenced by the physiological state of an organism.
Both sleep deprivation and changes in satiety are connected with changes in the function of the
olfactory system. Physiological changes such as these are integrated in the hypothalamus, where
different neuropeptides are expressed by specific populations of neurons. These peptides can
regulate transitions between wakefulness and sleep, or promote feeding behaviors. One peptide
that functions in both promoting feeding and sleep is melanin-concentrating hormone (MCH).
Neurons expressing MCH project to several areas of the brain including the olfactory bulb (OB),
where the MCH receptor, MCHR1, is expressed. This connection represents a previously
understudied pathway providing a potential mechanism for sleep or satiety induced changes in
olfactory function. The proposed research will investigate the role of MCH signaling and
hypothalamic MCH neurons in contributing to odor processing. The aims of this proposal will test
the central hypothesis centrifugal MCH neurons integrate physiological states and regulate
olfactory function. Aim 1 will use molecular and biochemical techniques to investigate changes in
MCH levels in the OB in response to food restriction. It will also use complementary mouse
models to determine the cellular targets of hypothalamic MCH neurons in olfactory regions. Aim
2 will investigate the effects of MCH on the activity of mitral cells in the olfactory bulb, and how
changes in MCH effect odor threshold detection and cross-habituation in animals that lack
components of the MCH signaling pathway. It will also test how activation of hypothalamic MCH
neurons modulates these behaviors. Using AAV mediated approaches, we will target MCHR1
removal specifically in the OB to isolate its contribution to regulating behavioral changes. Finally,
in Aim 3 we will investigate how disruption of primary cilia, the cellular site of MCHR1
localization, on neurons in the OB impacts an animal's ability to detect and discriminate odors.
Completion of the proposed studies will provide new mechanistic insight into the role of the lateral
hypothalamus in regulating olfactory function. The results from the proposed research will be
important for understanding how changes in satiety or in wakefulness can impact the sense of
smell. It will also provide insight into mechanisms of sensory dysfunction that occur in some
ciliopathy patients. Completion of this project will establish future experiments to address the
molecular mechanisms of MCH modulation in the OB.
项目概要
嗅觉对于维持人类的健康和生活质量至关重要。它扮演一个
在检测环境危险以及指导决策方面发挥着重要作用,例如
吃的食物。然而,嗅觉处理受到生物体生理状态的影响。
睡眠不足和饱腹感的变化都与大脑功能的变化有关。
嗅觉系统。诸如此类的生理变化被整合到下丘脑中,其中
不同的神经肽由特定的神经元群表达。这些肽可以
调节清醒和睡眠之间的过渡,或促进进食行为。一种肽
黑色素浓缩激素(MCH)具有促进进食和睡眠的作用。
表达 MCH 的神经元投射到大脑的多个区域,包括嗅球 (OB)、
其中表达 MCH 受体 MCHR1。该连接代表先前的
正在研究的途径为睡眠或饱腹感引起的变化提供了潜在机制
嗅觉功能。拟议的研究将调查 MCH 信号传导的作用和
下丘脑 MCH 神经元参与气味处理。该提案的目标将测试
中心假设离心MCH神经元整合生理状态并调节
嗅觉功能。目标 1 将使用分子和生化技术来研究
OB 中的 MCH 水平对食物限制的反应。它还将使用互补鼠标
确定嗅觉区域下丘脑 MCH 神经元细胞靶标的模型。目的
2 将研究 MCH 对嗅球二尖瓣细胞活性的影响,以及如何影响
MCH 的变化影响气味阈值检测和缺乏气味的动物的交叉习惯
MCH 信号通路的组成部分。它还将测试下丘脑 MCH 的激活如何
神经元调节这些行为。使用 AAV 介导的方法,我们将针对 MCHR1
特别是在 OB 中去除,以隔离其对调节行为变化的贡献。最后,
在目标 3 中,我们将研究如何破坏初级纤毛(MCHR1 的细胞位点)
OB 神经元上的定位会影响动物检测和辨别气味的能力。
完成拟议的研究将为横向作用提供新的机制见解
下丘脑调节嗅觉功能。拟议研究的结果将是
对于理解饱腹感或清醒度的变化如何影响感觉很重要
闻。它还将提供对某些疾病中发生的感觉功能障碍机制的深入了解。
纤毛病患者。该项目的完成将建立未来的实验来解决
OB 中 MCH 调节的分子机制。
项目成果
期刊论文数量(3)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Neuronal primary cilia integrate peripheral signals with metabolic drives.
- DOI:10.3389/fphys.2023.1150232
- 发表时间:2023
- 期刊:
- 影响因子:4
- 作者:
- 通讯作者:
{{
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 }}
Karina Alvina其他文献
Karina Alvina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 }}
相似海外基金
Acute senescence: a novel host defence counteracting typhoidal Salmonella
急性衰老:对抗伤寒沙门氏菌的新型宿主防御
- 批准号:
MR/X02329X/1 - 财政年份:2024
- 资助金额:
$ 31.68万 - 项目类别:
Fellowship
Transcriptional assessment of haematopoietic differentiation to risk-stratify acute lymphoblastic leukaemia
造血分化的转录评估对急性淋巴细胞白血病的风险分层
- 批准号:
MR/Y009568/1 - 财政年份:2024
- 资助金额:
$ 31.68万 - 项目类别:
Fellowship
Combining two unique AI platforms for the discovery of novel genetic therapeutic targets & preclinical validation of synthetic biomolecules to treat Acute myeloid leukaemia (AML).
结合两个独特的人工智能平台来发现新的基因治疗靶点
- 批准号:
10090332 - 财政年份:2024
- 资助金额:
$ 31.68万 - 项目类别:
Collaborative R&D
Cellular Neuroinflammation in Acute Brain Injury
急性脑损伤中的细胞神经炎症
- 批准号:
MR/X021882/1 - 财政年份:2024
- 资助金额:
$ 31.68万 - 项目类别:
Research Grant
KAT2A PROTACs targetting the differentiation of blasts and leukemic stem cells for the treatment of Acute Myeloid Leukaemia
KAT2A PROTAC 靶向原始细胞和白血病干细胞的分化,用于治疗急性髓系白血病
- 批准号:
MR/X029557/1 - 财政年份:2024
- 资助金额:
$ 31.68万 - 项目类别:
Research Grant
Combining Mechanistic Modelling with Machine Learning for Diagnosis of Acute Respiratory Distress Syndrome
机械建模与机器学习相结合诊断急性呼吸窘迫综合征
- 批准号:
EP/Y003527/1 - 财政年份:2024
- 资助金额:
$ 31.68万 - 项目类别:
Research Grant
FITEAML: Functional Interrogation of Transposable Elements in Acute Myeloid Leukaemia
FITEAML:急性髓系白血病转座元件的功能研究
- 批准号:
EP/Y030338/1 - 财政年份:2024
- 资助金额:
$ 31.68万 - 项目类别:
Research Grant
STTR Phase I: Non-invasive focused ultrasound treatment to modulate the immune system for acute and chronic kidney rejection
STTR 第一期:非侵入性聚焦超声治疗调节免疫系统以治疗急性和慢性肾排斥
- 批准号:
2312694 - 财政年份:2024
- 资助金额:
$ 31.68万 - 项目类别:
Standard Grant
ロボット支援肝切除術は真に低侵襲なのか?acute phaseに着目して
机器人辅助肝切除术真的是微创吗?
- 批准号:
24K19395 - 财政年份:2024
- 资助金额:
$ 31.68万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
Acute human gingivitis systems biology
人类急性牙龈炎系统生物学
- 批准号:
484000 - 财政年份:2023
- 资助金额:
$ 31.68万 - 项目类别:
Operating Grants