The Glycine Receptor in a Rat Tinnitus Model: A Possible Therapeutic Target
The Glycine Receptor in a Rat Tinnitus Model: A Possible Therapeutic Target
批准号:
8090310
负责人:
Donald M. Caspary
金额:
$29.04万
依托单位国家:
美国
项目类别:
财政年份:
2007
资助国家:
美国
项目状态:
已结题
起止时间:
2007-07-01 至 2013-06-30
关键词:
AffinityAgeAgingAnimal ModelAnimalsAppearanceAuditoryAuditory systemAutoradiographyBehavioralBindingBrain-Derived Neurotrophic FactorCell surfaceChronicCochleaDeafferentation procedureDetectionDevelopmentDoseElderlyElectrodesEsthesiaEventFrequenciesFunctional disorderFusiform CellGenerationsGlycineGlycine Receptor BindingGlycine ReceptorsHyperactive behaviorIn Situ HybridizationIncidenceLabelLaboratoriesLeadLinkLongevityMeasuresModelingMolecularNerve Growth Factor ReceptorsNeuronsNeurotrophic Tyrosine Kinase Receptor Type 2NoiseOutputPatternPeripheralPharmaceutical PreparationsPharmacologyPlasticsPopulationPropertyProtein SubunitsProteinsQuality of lifeRadiolabeledRattusResearch PersonnelRoleScaffolding ProteinSeriesStructureStrychnineSurgical DisarticulationTestingTherapeuticThinkingTinnitusTraumaWestern BlottingWorkage relatedageddorsal cochlear nucleusexperiencegephyrinimmunocytochemistryinsightjuvenile animalneurochemistryneurotransmissionneurotrophic factornovelprogramsradiotracerreceptorreceptor bindingreceptor sensitivityrelating to nervous systemresponsesensory systemsoundtherapeutic targetyoung adult
中文摘要
描述(申请人提供):慢性耳鸣是一种幻觉的听觉感觉,高达15%的人口经历。2%到10%的耳鸣患者通常会经历持续的高频振铃或嘶嘶声,其响度足以严重影响他们的生活质量(Cooper,1994)。耳鸣已被发现随着年龄的增长而增加。因此,由于寿命延长和娱乐性噪音暴露,耳鸣的发生率可能会增加。目前关于耳鸣发生的许多想法都围绕着某些中枢听觉结构中自发活动和神经过度活动的出现。一个与其他感觉系统的研究结果类似的工作假说表明,部分去传入会导致中枢变化,通常涉及到抑制性神经传递的改变。部分外周听觉去传入可引起耳鸣,同时耳蜗背核(DCN)选择性丧失抑制性甘氨酸能功能。拟议的研究将检查衰老对有耳鸣行为证据的大鼠的功能和分子神经化学影响。初步结果发现,在有耳鸣行为证据的大鼠DCN中,与年龄和噪声暴露相关的甘氨酸受体和神经营养因子神经化学改变。拟议的研究将比较年轻和老年对照组以及年轻和老年暴露于声音中的大鼠与耳鸣的行为证据之间的功能和分子神经化学变化。具体地说:1)信息和蛋白质的定量测量将被用来检测甘氨酸受体、支架蛋白、地理卟啉和保护性神经营养因子BDNF组成的亚单位的变化;2)来自DCN梭形细胞的记录将平行于行为学研究/间隙检测,并检查抑制反应特性和甘氨酸受体的敏感性;3)定量受体结合将被用于检测甘氨酸和神经营养因子受体药理学的变化。这些研究的结果将提供有关耳鸣相关的甘氨酸神经传递的变化以及在耳鸣动物模型中可能的神经营养素保护的新信息。了解衰老对与甘氨酸和脑源性神经营养因子受体(TrkB)功能相关的神经化学改变的影响,可能有助于为治疗耳鸣的新型选择性药物的开发和测试确定独特的靶点。
英文摘要
DESCRIPTION (provided by applicant): Chronic tinnitus is a phantom auditory sensation experienced by up to 15% of the population. Between 2 and 10% of the tinnitus population typically experience a continuous high frequency ringing or hiss sufficiently loud to impact severely on their quality of life (Cooper, 1994). Tinnitus has been found to increase with aging. Thus, the incidence of tinnitus is likely to increase due to increased longevity and recreational noise exposure. Much of the present thinking regarding the generation of tinnitus revolves around the appearance of spontaneous activity and neural hyperactivity in certain central auditory structures. A working hypothesis which parallels findings in other sensory systems suggests that partial deafferentation leads to central changes, generally involving altered inhibitory neurotransmission. Partial peripheral auditory deafferentation may produce tinnitus, coincident with a selective loss of inhibitory glycinergic function in the dorsal cochlear nucleus (DCN). Proposed studies will examine the functional and molecular neurochemical impact of aging in rats with behavioral evidence of tinnitus. Preliminary results find age and noise-exposure related changes in glycine receptor and neurotrophic factor neurochemistry in DCN of rats with behavioral evidence of tinnitus. Proposed studies will compare functional and molecular neurochemical changes between young and aged controls, and young and aged sound-exposed rats with behavioral evidence of tinnitus. Specifically: 1) quantitative measures of message and protein will be used to examine changes in the subunit make up of the glycine receptor, the scaffolding protein, gephyrin, and the protective neurotrophin BDNF; 2) recordings from DCN fusiform cells will parallel behavioral studies/gap detection and examine inhibitory response properties and glycine receptor sensitivity and 3) quantitative receptor binding will be used to examine changes in glycine and neurotrophin receptor pharmacology. Findings from these studies will provide new information regarding tinnitus-related changes in glycine neurotransmission and possible neurotrophin protection in an animal model of tinnitus. Understanding the impact of aging on tinnitus-related changes in neurochemistry related to glycine and the BDNF receptor (TrkB) function might help define unique targets for the development and testing of novel selective drugs for the treatment of tinnitus.
期刊论文(9)
专著(0)
科研奖励(0)
会议论文
登录
查看更多内容
Extrasynaptic GABA(A) receptors and tonic inhibition in rat auditory thalamus.
大鼠听觉丘脑的突触外 GABA(A) 受体和强直抑制。
DOI:
10.1371/journal.pone.0016508
发表时间:
2011
期刊:
PloS one
影响因子:
3.7
作者:
[Richardson,BenD, Ling,LynneL, Uteshev,VictorV, Caspary,DonaldM]
通讯作者:
Caspary,DonaldM
DOI:
10.1016/j.brainres.2012.02.014
发表时间:
2012-11-16
期刊:
Brain research
影响因子:
2.9
作者:
[Richardson BD, Brozoski TJ, Ling LL, Caspary DM]
通讯作者:
Caspary DM
DOI:
10.1016/j.neuroscience.2009.08.026
发表时间:
2009-12-01
期刊:
NEUROSCIENCE
影响因子:
3.3
作者:
[Wang, H., Brozoski, T. J., Turner, J. G., Ling, L., Parrish, J. L., Hughes, L. F., Caspary, D. M.]
通讯作者:
Caspary, D. M.
DOI:
10.1016/j.heares.2011.04.004
发表时间:
2011-09
期刊:
HEARING RESEARCH
影响因子:
2.8
作者:
[Wang, Hongning, Brozoski, Thomas J., Caspary, Donald M.]
通讯作者:
Caspary, Donald M.
DOI:
10.1523/jneurosci.2499-12.2012
发表时间:
2012-11-14
期刊:
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子:
--
作者:
[Llano DA, Turner J, Caspary DM]
通讯作者:
Caspary DM
共 8 条
The Glycine Receptor in a Rat Tinnitus Model: A Possible Therapeutic Target
-
批准号:7850333
-
项目类别:
-
资助金额:$3.8万
-
财政年份:2009
-
负责人:Donald M. Caspary
-
依托单位:
The Glycine Receptor in a Rat Tinnitus Model: A Possible Therapeutic Target
-
批准号:7845121
-
项目类别:
-
资助金额:$0.71万
-
财政年份:2009
-
负责人:Donald M. Caspary
-
依托单位:
The Glycine Receptor in a Rat Tinnitus Model: A Possible Therapeutic Target
-
批准号:7371960
-
项目类别:
-
资助金额:$30.31万
-
财政年份:2007
-
负责人:Donald M. Caspary
-
依托单位:
The Glycine Receptor in a Rat Tinnitus Model: A Possible Therapeutic Target
-
批准号:7625935
-
项目类别:
-
资助金额:$30.31万
-
财政年份:2007
-
负责人:Donald M. Caspary
-
依托单位:
The Glycine Receptor in a Rat Tinnitus Model: A Possible Therapeutic Target
-
批准号:7260572
-
项目类别:
-
资助金额:$30.71万
-
财政年份:2007
-
负责人:Donald M. Caspary
-
依托单位:
The Glycine Receptor in a Rat Tinnitus Model: A Possible Therapeutic Target
-
批准号:7879990
-
项目类别:
-
资助金额:$30.0万
-
财政年份:2007
-
负责人:Donald M. Caspary
-
依托单位:
CODING IN AUDITORY NEURONS--EFFECTS OF AMINO ACIDS
-
批准号:2733627
-
项目类别:
-
资助金额:$17.28万
-
财政年份:1979
-
负责人:Donald M. Caspary
-
依托单位:
Coding in Auditory Neurons: Effects of Amino Acids
-
批准号:6640280
-
项目类别:
-
资助金额:$32.08万
-
财政年份:1979
-
负责人:Donald M. Caspary
-
依托单位:
Coding in Auditory Neurons: Effects of Amino Acids
-
批准号:8019696
-
项目类别:
-
资助金额:$12.83万
-
财政年份:1979
-
负责人:Donald M. Caspary
-
依托单位:
Coding in Auditory Neurons: Effects of Amino Acids
-
批准号:8305089
-
项目类别:
-
资助金额:$26.94万
-
财政年份:1979
-
负责人:Donald M. Caspary
-
依托单位:
Coding in Auditory Neurons: Effects of Amino Acids
-
批准号:8719742
-
项目类别:
-
资助金额:$26.94万
-
财政年份:1979
-
负责人:Donald M. Caspary
-
依托单位:
CODING IN AUDITORY NEURONS--EFFECTS OF AMINO ACIDS
-
批准号:2124852
-
项目类别:
-
资助金额:$15.85万
-
财政年份:1979
-
负责人:Donald M. Caspary
-
依托单位:
CODING IN AUDITORY NEURONS: EFFECTS OF AMINO ACIDS
-
批准号:3396381
-
项目类别:
-
资助金额:$8.48万
-
财政年份:1979
-
负责人:Donald M. Caspary
-
依托单位:
CODING IN AUDITORY NEURONS--EFFECTS OF AMINO ACIDS
-
批准号:6030123
-
项目类别:
-
资助金额:$17.8万
-
财政年份:1979
-
负责人:Donald M. Caspary
-
依托单位:
CODING IN AUDITORY NEURONS: EFFECTS OF AMINO ACIDS
-
批准号:3215893
-
项目类别:
-
资助金额:$14.13万
-
财政年份:1979
-
负责人:Donald M. Caspary
-
依托单位:
CODING IN AUDITORY NEURONS--EFFECTS OF AMINO ACIDS
-
批准号:3215892
-
项目类别:
-
资助金额:$13.56万
-
财政年份:1979
-
负责人:Donald M. Caspary
-
依托单位:
Coding in Auditory Neurons: Effects of Amino Acids
-
批准号:9026275
-
项目类别:
-
资助金额:$52.22万
-
财政年份:1979
-
负责人:Donald M. Caspary
-
依托单位:
CODING IN AUDITORY NEURONS: EFFECTS OF AMINO ACIDS
-
批准号:3396383
-
项目类别:
-
资助金额:$9.45万
-
财政年份:1979
-
负责人:Donald M. Caspary
-
依托单位:
CODING IN AUDITORY NEURONS EFFECTS OF AMINO ACIDS
-
批准号:3396382
-
项目类别:
-
资助金额:$5.08万
-
财政年份:1979
-
负责人:Donald M. Caspary
-
依托单位:
CODING IN AUDITORY NEURONS--EFFECTS OF AMINO ACIDS
-
批准号:6175788
-
项目类别:
-
资助金额:$18.33万
-
财政年份:1979
-
负责人:Donald M. Caspary
-
依托单位:
国内基金
海外基金
登录
查看更多内容
补阳还五汤通过AGE-RAGE通路调控脓毒症免疫失衡的机制与转化研究
-
批准号:JCZRLH202601523
-
项目类别:省市级项目
-
资助金额:--
-
批准年份:2026
-
负责人:
-
依托单位:
靶向递送一氧化碳调控AGE-RAGE级联反应促进糖尿病创面愈合研究
-
批准号:JCZRQN202500010
-
项目类别:省市级项目
-
资助金额:--
-
批准年份:2025
-
负责人:
-
依托单位:
对香豆酸抑制AGE-RAGE-Ang-1通路改善海马血管生成障碍发挥抗阿尔兹海默病作用
-
批准号:2025JJ70209
-
项目类别:省市级项目
-
资助金额:--
-
批准年份:2025
-
负责人:雷芬芳
-
依托单位:
AGE-RAGE通路调控慢性胰腺炎纤维化进程的作用及分子机制
-
批准号:--
-
项目类别:面上项目
-
资助金额:--
-
批准年份:2024
-
负责人:万荣
-
依托单位:
甜茶抑制AGE-RAGE通路增强突触可塑性改善小鼠抑郁样行为
-
批准号:2023JJ50274
-
项目类别:省市级项目
-
资助金额:--
-
批准年份:2023
-
负责人:贺志明
-
依托单位:
蒙药额尔敦-乌日勒基础方调控AGE-RAGE信号通路改善术后认知功能障碍研究
-
批准号:--
-
项目类别:地区科学基金项目
-
资助金额:33万元
-
批准年份:2022
-
负责人:都义日
-
依托单位:
补肾健脾祛瘀方调控AGE/RAGE信号通路在再生障碍性贫血骨髓间充质干细胞功能受损的作用与机制研究
-
批准号:--
-
项目类别:面上项目
-
资助金额:52万元
-
批准年份:2022
-
负责人:叶宝东
-
依托单位:
LncRNA GAS5在2型糖尿病动脉粥样硬化中对AGE-RAGE 信号通路上相关基因的调控作用及机制研究
-
批准号:
-
项目类别:省市级项目
-
资助金额:10.0万元
-
批准年份:2022
-
负责人:于海兵
-
依托单位:
围绕GLP1-Arginine-AGE/RAGE轴构建探针组学方法探索大柴胡汤异病同治的效应机制
-
批准号:81973577
-
项目类别:面上项目
-
资助金额:55.0万元
-
批准年份:2019
-
负责人:辛贵忠
-
依托单位:
AGE/RAGE通路microRNA编码基因多态性与2型糖尿病并发冠心病的关联研究
-
批准号:81602908
-
项目类别:青年科学基金项目
-
资助金额:18.0万元
-
批准年份:2016
-
负责人:刘括
-
依托单位: