Peripheral auditory system deficits and autism-like behaviors
周围听觉系统缺陷和自闭症样行为
基本信息
- 批准号:10349592
- 负责人:
- 金额:$ 19.93万
- 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 2024-03-31
- 项目状态:已结题
- 来源:
- 关键词:Abnormal MacrophageAcoustic NerveAddressAge related macular degenerationAnimal ModelAnimalsAntibioticsArginineAuditoryAuditory Brainstem ResponsesAuditory PerceptionAuditory systemAwardBehaviorBehavior DisordersBrainCBA/CaJ MouseCellsChildCochleaCollaborationsCommunicationCommunication impairmentCompanionsComplementComplement 3aComplement 3d ReceptorsComplement ActivationComplement Factor HDevelopmentDiseaseDisease modelEnhancersExhibitsFDA approvedFunctional disorderGenesGoalsHearingHearing problemHumanImmuneImmune System DiseasesImpairmentIndividualInvestigationK-18 conjugateKnowledgeLaboratoriesLifestyle-related conditionLinkMacrophage ActivationMeasurementMeasuresMedicalMentorsMentorshipMicrogliaMinocyclineMolecular ProfilingMusMuscle CellsMutationNational Institute on Deafness and Other Communication DisordersNerve DegenerationNerve FibersNervous system structureNeurodevelopmental DisorderNeuroimmuneNeuronsPathologicPathologyPathway interactionsPeripheralPharmacologyPharmacotherapyPhysiologicalPlayPopulationQuality of lifeRecovery of FunctionReportingResearchResearch ActivityResearch Project GrantsRiskRoleSchool Health ServicesScientific Advances and AccomplishmentsSensorineural Hearing LossSocial BehaviorSocial InteractionSocializationSouth CarolinaSymptomsSyndromeTestingTetracyclinesTherapeuticTrainingTraining ActivityUltrasonicsUniversitiesWild Type MouseWorkantagonistauditory processingautism spectrum disorderautisticbasebehavioral impairmentbehavioral phenotypingcareercommon symptomconditional mutantdemographicsdevelopmental diseasedisabilityexperienceexperimental studyfunctional declinehearing impairmenthuman modelhuman subjectindividuals with autism spectrum disorderinhibitorinnovationmacrophagemedical schoolsmouse modelmutant mouse modelneuroimmunologynovelpostnatalprogramsreceptorrelating to nervous systemresponsesocialsocial communicationtooltreatment strategyvocalization
项目摘要
SUMMARY
Children with hearing loss have an increased risk for developing other disabilities. One commonly associated
disability is Autism Spectrum Disorder (ASD), a condition that also includes alterations in the auditory system.
Hearing loss might contribute to ASD core symptoms and interfere with communication, social interaction, and
overall quality of life. Nearly 1 in 59 children with hearing loss were reported to receive school-based services
for ASD. Mutations or deletions in the Myocyte-specific Enhancer Factor 2C (MEF2C) gene have recently been
linked to ASD and other neurodevelopmental disorders. A preliminary study conducted in the candidate’s
laboratory found that (1) Mef2c is highly expressed in auditory nerve macrophages in postnatal wild type mice,
and (2) auditory nerve functional decline and hearing loss occur in a novel mouse model of a syndromic autism
disorder, human MEF2C haploinsufficiency syndrome. The overall goal of this NIDCD Research Career
Enhancement Award (K18) resubmission is to augment the candidate’s research expertise to study how
peripheral auditory system deficits contribute to communication and other social behavior impairments in ASD
and other common human developmental disorders. The candidate is an established auditory neuroscientist
with more than 20 years of experience in the pathophysiology of the peripheral auditory system and resultant
sensorineural hearing loss. With the mentorship of four leading experts from the Medical University of South
Carolina and Harvard Medical School, the training plan and research project will provide the opportunity for the
candidate to (1) acquire advanced scientific knowledge/research tools in the fields of neuroimmunology,
neurodevelopmental disorders, central auditory processing and perception, and communication and social
interaction behaviors; and (2) conduct a study to address the novel hypothesis that abnormal macrophage
activity resulting from Mef2c deficiency leads to AN functional declines and hearing loss, and that these
changes may be associated with abnormalities in higher levels of the nervous system and contribute to
communication impairment and other autistic symptoms. These training and research activities will catalyze
research collaborations in new directions and establish innovative research programs to study hearing loss and
communication impairment in human neurodevelopmental disorders. These investigations will promote a
greater understanding of the important role of cochlear macrophage and auditory nerve dysfunction in ASD
and other neurodevelopmental disorders, and may reveal a neuro-immune based therapeutic strategy
beneficial for this fast growing population.
概括
患有听力损失的儿童患其他常见残疾的风险会增加。
残疾属于自闭症谱系障碍 (ASD),这种疾病还包括听觉系统的改变。
听力损失可能会导致自闭症谱系障碍 (ASD) 核心症状,并干扰沟通、社交互动和
据报告,近五分之一的听力损失儿童接受了学校服务。
最近发现了肌细胞特异性增强因子 2C (MEF2C) 基因的突变或缺失。
与自闭症谱系障碍和其他神经发育障碍有关的一项针对候选人的初步研究。
实验室发现(1)Mef2c在产后野生型小鼠的听神经巨噬细胞中高表达,
(2) 新型自闭症小鼠模型中出现听神经功能衰退和听力丧失
疾病,人类 MEF2C 单倍体不足综合征 NIDCD 研究生涯的总体目标。
增强奖(K18)重新提交是为了增强候选人的研究专业知识,以研究如何
周围听觉系统缺陷会导致自闭症谱系障碍患者的沟通和其他社会行为障碍
和其他常见的人类发育障碍。候选人是一位成熟的听觉神经科学家。
在外周听觉系统的病理生理学及其研究方面拥有 20 多年的经验
在南方医科大学四位领先专家的指导下。
卡罗莱纳州和哈佛医学院的培训计划和研究项目将为
候选人(1)获得神经免疫学领域的先进科学知识/研究工具,
神经发育障碍、中枢听觉处理和感知、沟通和社交
相互作用行为;(2) 进行一项研究来解决异常巨噬细胞的新假设
Mef2c 缺乏导致的活动会导致 AN 功能下降和听力损失,并且这些
变化可能与神经系统高级水平的异常有关,并有助于
这些培训和研究活动将促进沟通障碍和其他自闭症症状。
新方向的研究合作并建立创新研究计划来研究听力损失和
这些研究将促进人类神经发育障碍中的沟通障碍。
更好地了解耳蜗巨噬细胞和听神经功能障碍在 ASD 中的重要作用
和其他神经发育障碍,并可能揭示基于神经免疫的治疗策略
对这个快速增长的人口有利。
项目成果
期刊论文数量(0)
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{{ truncateString('Hainan Lang', 18)}}的其他基金
Peripheral auditory system deficits and autism-like behaviors
周围听觉系统缺陷和自闭症样行为
- 批准号:
10187095 - 财政年份:2021
- 资助金额:
$ 19.93万 - 项目类别:
Cell survival and cell death in the auditory nerve
听神经中的细胞存活和细胞死亡
- 批准号:
7352782 - 财政年份:2006
- 资助金额:
$ 19.93万 - 项目类别:
Cell survival and cell death in the auditory nerve
听神经中的细胞存活和细胞死亡
- 批准号:
7178505 - 财政年份:2006
- 资助金额:
$ 19.93万 - 项目类别:
Cell survival and cell death in the auditory nerve
听神经中的细胞存活和细胞死亡
- 批准号:
7035117 - 财政年份:2006
- 资助金额:
$ 19.93万 - 项目类别:
Project 2: Mechanistic studies of age-related hearing loss using animal models and human tissue
项目2:利用动物模型和人体组织研究年龄相关性听力损失的机制
- 批准号:
10470232 - 财政年份:1997
- 资助金额:
$ 19.93万 - 项目类别:
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