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Defining the Autonomic Cerebellum in Autism

定义自闭症自主小脑

基本信息

批准号：
10696307
负责人：
Ronald Robert Seese
金额：
$ 39万
依托单位：
NORTHEAST OHIO MEDICAL UNIVERSITY
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：
2023-09-21 至 2028-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10696307
关键词：
Adrenal Glands Adrenal Medulla Affect Anatomy Animals Area Award Behavior Behavioral Blood Pressure Brain Brain region Budgets Callithrix Cerebellar vermis structure Cerebellum Clinical Communities Core Facility Dedications Development Disease Dysautonomias Educational process of instructing Ensure Epinephrine Exhibits Exposure to Extramural Activities Faculty Family Foundations Funding Galvanic Skin Response Goals Heart Rate Human Institution Knowledge Length Lobule Location Medical Mentors Mentorship Modeling Molecular Monkeys Neuroanatomy Neurobiology Neurodevelopmental Disorder Neurologist Neurology Neurosciences Nurses Ohio Organ Output Patients Pediatric Hospitals Pediatrics Peer Review Peripheral Physiological Productivity Psychiatry Publications Rabies virus Refractory Research Research Assistant Research Training Resources Risk Science Secure Site Source System Testing Transcranial magnetic stimulation Translating Universities Valproic Acid Vision Work animal facility autism spectrum disorder autistic children clinical training clinical translation clinically relevant density design disability faculty mentor graduate student in vivo individuals with autism spectrum disorder innovative technologies member multidisciplinary neural network neuronal transport neuroregulation nonhuman primate novel novel therapeutic intervention novel therapeutics prenatal exposure prevent programs response senior faculty side effect skills square foot targeted treatment tenure track therapeutic target translational research program waiver

项目摘要

PROJECT SUMMARY/ABSTRACT Autism spectrum disorder (ASD) is a prevalent and disabling neurodevelopmental disorder that takes a significant toll on patients, their families, and the national economy. There are no targeted treatments for the dysregulated autonomic responses, or dysautonomia, that affect and disable over 70% of autistic children. Most current medical approaches are non-selective, ineffective, and associated with side effects. Thus, a novel and targeted therapy is urgently needed for refractory dysautonomia in ASD. Given dysautonomia is thought to arise from a problem in how the brain regulates peripheral autonomic organs, a major barrier to progress has been an incomplete understanding of the neural networks that influence peripheral autonomic output. Recently, I identified the sites of the cerebellum that are major sources of descending control over the adrenal medulla, an autonomic organ that releases adrenaline and initiates the body-wide sympathetic response. Cerebellar involvement is clinically relevant because dysautonomia and cerebellar abnormalities are both present in ASD and the superficial location of the cerebellum makes it an attractive target for non-invasive trans-cranial magnetic stimulation (TMS). Yet, two remaining knowledge gaps prevent clinical translation: we do not know which sites of the ‘autonomic cerebellum’ influence the physiologic responses perturbed in dysautonomia and how these sites are affected in conditions like ASD where dysautonomia and cerebellar abnormalities are present. The goals of this project are to fill these gaps by defining the regions of the autonomic cerebellum that selectively control physiologic responses and by testing how these cerebellar networks are altered in a model of autism. Specifically, Aim 1 is to test if modulating the adrenal-related cerebellum alters autonomic physiologic responses. Aim 2 is to test if autonomic responses are abnormal in a marmoset model of ASD. Aim 3 is to test if the cerebellar sites that control the adrenal’s sympathetic output are altered in a marmoset model of ASD. I will employ in vivo recording of autonomic physiologic responses and trans-neuronal transport of rabies virus to establish the behavioral and systems neuroscience foundations for how the autonomic cerebellum is affected in ASD. These studies have the potential to identify specific cerebellar regions to target with a new treatment approach (e.g., cerebellar TMS) that aims to normalize refractory dysautonomia in ASD. Thus, the results of the proposed work may ultimately transform how we manage dysautonomia in ASD and other disorders associated with cerebellar abnormalities.

项目总结/文摘