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Limbic-basal ganglia connectivity in a non-human primate model of Huntington's disease

亨廷顿病非人类灵长类动物模型中的边缘-基底神经节连接

基本信息

批准号：
9811798
负责人：
Alison Ruth Weiss
金额：
$ 4.43万
依托单位：
OREGON HEALTH & SCIENCE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-30 至 2020-06-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9811798
关键词：
Address Adult Affect Affective Aggressive behavior Amygdaloid structure Anatomy Anhedonia Animal Disease Models Anterior Anxiety Area Atrophic Award Basal Ganglia Behavioral Behavioral Assay Brain CAG repeat Caregivers Chromosomes, Human, Pair 4 Cognitive Corpus striatum structure Dependovirus Depression and Suicide Development Diffusion Magnetic Resonance Imaging Disease Disease Progression Disease model Emotional Faculty Fellowship Fiber Functional Magnetic Resonance Imaging Funding Future Gene Mutation Genes Goals Histologic Histological Techniques Human Huntington Disease Huntington protein Hyperactive behavior Image Impaired cognition Impairment Inclusion Bodies Inherited Injections Intervention Knowledge Laboratories Light Limbic System Macaca mulatta Magnetic Resonance Imaging Measures Mediating Mentors Modeling Molecular Molecular Analysis Moods Motor Movement Disorders Mutation National Institute of Neurological Disorders and Stroke National Research Service Awards Nerve Degeneration Neurobehavioral Manifestations Neurodegenerative Disorders Neuroglia Neurons Neurosciences Neurosciences Research Operative Surgical Procedures Pathologic Patients Personality Phenotype Production Psychiatric therapeutic procedure Quality of life Reporting Research Rest Stretching Structure Sucrose Sum Symptoms Techniques Technology Testing Therapeutic Therapeutic Intervention Time United States National Institutes of Health Western Blotting brain circuitry cingulate cortex cognitive function cognitive neuroscience density disturbance in affect emotion regulation gain of function in vivo interest mRNA Expression member mood symptom motor deficit motor symptom multidisciplinary mutant neuroimaging neuromechanism neuropathology nonhuman primate novel preference prospective protein aggregate protein expression psychiatric symptom putamen retrograde transport skills tenure track therapeutic development white matter

项目摘要

Huntington's disease (HD) is a degenerative neurological disorder caused by an expanded CAG repeat sequence in the dominantly-inherited HTT gene on chromosome 4. When the CAG repeat stretch exceeds 40 repeats the encoded mutant huntingtin protein (mHTT) misfolds, resulting in a toxic gain of function that is neurodegenerative. HD symptoms are detrimental to the patient's quality of life, as they suffer from a progressive hyperkinetic movement disorder accompanied by deteriorating cognitive function and profound personality changes/mood disturbances. The emotional and physical burden on both the patient and the caregiver are tremendous, and patients often report their mood symptoms to be the most burdensome to both themselves and their caretakers. To address this need, the central goal of my project will be to characterize the impact of HD neuropathology on limbic-basal ganglia connectivity and behavioral phenotypes relevant to the mood/psychiatric symptoms. I will use behavioral assays to assess mood and affect in our HD animal model, and I will perform neuroimaging, histological, and molecular analyses, focusing on specific regions of interest in limbic (amygdala, anterior cingulate cortex, orbitofrontal cortex) and basal ganglia (caudate and putamen) regions. In sum, I will take a multifaceted approach using both in vivo (neuroimaging and behavioral assays in Aim 1 and 2) and ex vivo (histological and molecular in Aim 3) techniques. The strength of my studies lays in their ability to identify prospective neuroimaging changes that can be connected with a wide array of behavioral and neuropathological phenotypes of HD.

亨廷顿氏病（HD）是一种由CAG重复扩增引起的退行性神经系统疾病