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：
Hainan Lang
金额：
$ 19.93万
依托单位：
MEDICAL UNIVERSITY OF SOUTH CAROLINA
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：
https://reporter.nih.gov/project-details/10349592
关键词：
Abnormal Macrophage Acoustic Nerve Address Age related macular degeneration Animal Model Animals Antibiotics Arginine Auditory Auditory Brainstem Responses Auditory Perception Auditory system Award Behavior Behavior Disorders Brain CBA/CaJ Mouse Cells Child Cochlea Collaborations Communication Communication impairment Companions Complement Complement 3a Complement 3d Receptors Complement Activation Complement Factor H Development Disease Disease model Enhancers Exhibits FDA approved Functional disorder Genes Goals Hearing Hearing problem Human Immune Immune System Diseases Impairment Individual Investigation K-18 conjugate Knowledge Laboratories Lifestyle-related condition Link Macrophage Activation Measurement Measures Medical Mentors Mentorship Microglia Minocycline Molecular Profiling Mus Muscle Cells Mutation National Institute on Deafness and Other Communication Disorders Nerve Degeneration Nerve Fibers Nervous system structure Neurodevelopmental Disorder Neuroimmune Neurons Pathologic Pathology Pathway interactions Peripheral Pharmacology Pharmacotherapy Physiological Play Population Quality of life Recovery of Function Reporting Research Research Activity Research Project Grants Risk Role School Health Services Scientific Advances and Accomplishments Sensorineural Hearing Loss Social Behavior Social Interaction Socialization South Carolina Symptoms Syndrome Testing Tetracyclines Therapeutic Training Training Activity Ultrasonics Universities Wild Type Mouse Work antagonist auditory processing autism spectrum disorder autistic base behavioral impairment behavioral phenotyping career common symptom conditional mutant demographics developmental disease disability experience experimental study functional decline hearing impairment human model human subject individuals with autism spectrum disorder inhibitor innovation macrophage medical schools mouse model mutant mouse model neuroimmunology novel postnatal programs receptor relating to nervous system response social social communication tool treatment strategy vocalization

Abnormal Macrophage Acoustic Nerve Address Age related macular degeneration Animal Model Animals Antibiotics Arginine Auditory Auditory Brainstem Responses Auditory Perception Auditory system Award Behavior Behavior Disorders Brain CBA/CaJ Mouse Cells Child Cochlea Collaborations Communication Communication impairment Companions Complement Complement 3a Complement 3d Receptors Complement Activation Complement Factor H Development Disease Disease model Enhancers Exhibits FDA approved Functional disorder Genes Goals Hearing Hearing problem Human Immune Immune System Diseases Impairment Individual Investigation K-18 conjugate Knowledge Laboratories Lifestyle-related condition Link Macrophage Activation Measurement Measures Medical Mentors Mentorship Microglia Minocycline Molecular Profiling Mus Muscle Cells Mutation National Institute on Deafness and Other Communication Disorders Nerve Degeneration Nerve Fibers Nervous system structure Neurodevelopmental Disorder Neuroimmune Neurons Pathologic Pathology Pathway interactions Peripheral Pharmacology Pharmacotherapy Physiological Play Population Quality of life Recovery of Function Reporting Research Research Activity Research Project Grants Risk Role School Health Services Scientific Advances and Accomplishments Sensorineural Hearing Loss Social Behavior Social Interaction Socialization South Carolina Symptoms Syndrome Testing Tetracyclines Therapeutic Training Training Activity Ultrasonics Universities Wild Type Mouse Work antagonist auditory processing autism spectrum disorder autistic base behavioral impairment behavioral phenotyping career common symptom conditional mutant demographics developmental disease disability experience experimental study functional decline hearing impairment human model human subject individuals with autism spectrum disorder inhibitor innovation macrophage medical schools mouse model mutant mouse model neuroimmunology novel postnatal programs receptor relating to nervous system response social social communication tool treatment strategy vocalization

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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.

概括听力损失的儿童患有其他疾病的风险增加。一个通常相关的残疾是自闭症谱系障碍（ASD），该疾病还包括听觉系统中的改变。听力损失可能导致ASD核心症状和干扰沟通，社交互动和整体生活质量。据报道，近59名听力损失的儿童接受了学校的服务对于ASD。肌细胞特异性增强子因子2C（MEF2C）基因中的突变或缺失最近已成为与ASD和其他神经发育障碍有关。在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觉神经巨噬细胞中高度表达，（2）听觉神经功能下降和听力损失发生在综合症自闭症的新型小鼠模型中疾病，人类MEF2C单倍症综合征。 NIDCD研究生涯的总体目标增强奖（K18）的重新提交是增强候选人的研究专业知识，以研究如何外围听觉系统定义有助于ASD中的交流和其他社会行为障碍和其他常见的人类发育障碍。候选人是已建立的听觉神经科学家在外围听觉系统的病理生理学和结果方面拥有20多年的经验感官听力损失。在南部医科大学的四位主要专家的攻击下卡罗来纳州和哈佛医学院，培训计划和研究项目将为候选人（1）在神经免疫学领域获取先进的科学知识/研究工具，神经发育障碍，中央听觉处理和感知以及沟通与社会互动行为；（2）进行一项研究，以解决异常巨噬细胞的新假设 MEF2C缺乏症引起的活动导致功能性下降和听力损失，并且这些变化可能与较高神经系统水平的异常有关，并有助于沟通障碍和其他令人印象深刻的症状。这些培训和研究活动将催化朝新方向进行研究合作，并建立创新的研究计划，以研究听力损失和人类神经发育障碍的沟通障碍。这些调查将促进对耳蜗巨噬细胞和听觉神经功能障碍在ASD中的重要作用有更多了解和其他神经发育障碍，并可能揭示基于神经免疫的理论策略对这个快速增长的人口有益。