权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Supplement to TR01 Human cortical development and neural plasticity altered by trisomy 21

TR01 补充品 21 三体改变的人类皮质发育和神经可塑性

基本信息

批准号：
10670626
负责人：
ANITA BHATTACHARYYA
金额：
$ 18.62万
依托单位：
UNIVERSITY OF WISCONSIN-MADISON
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-09-12 至 2024-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10670626
关键词：
3-Dimensional Adult Affect Anatomy Award Biological Brain Cell Culture Techniques Cells Chromosome 21 Cognition Cognitive Complex Defect Dendritic Spines Development Developmental Process Disease Down Syndrome Electrophysiology (science)Ensure Equipment Exhibits Foundations Functional disorder Funding Future Genes Genetic Genetic Transcription Glutamates Hippocampus (Brain)Human Human Chromosomes Human Genetics Impaired cognition Impairment In Vitro Incubators Individual Induced pluripotent stem cell derived neurons Intellectual functioning disability Interneurons Intervention Lead Long-Term Potentiation Maintenance Mental Depression Modeling Molecular Molecular Profiling Motor Mus Neuronal Differentiation Neuronal Dysfunction Neuronal Plasticity Neurons Parents Pathway interactions Population Pregnancy Process Public Health Research Resources Sampling Signal Transduction Synapses Synaptic Transmission Synaptic plasticity Temporal Lobe Therapeutic Intervention Transcriptional Regulation Work base cell type cost design developmental disease developmental genetics excitatory neuron experimental study frontal lobe gamma-Aminobutyric Acid gene regulatory network induced pluripotent stem cell inhibitory neuron insight mouse development mouse model neurodevelopment neurogenesis neuron development neuronal excitability postnatal prenatal progenitor programs social stem cell differentiation stem cell model synaptogenesis three dimensional cell culture

项目摘要

ABSTRACT Down syndrome (DS, trisomy 21, T21), a complex multigene disorder and the most common genetic cause of intellectual disability. However, surprisingly little is known about the underlying mechanisms that lead to cognitive impairment in DS. There are fewer neurons in adult DS cortex and reduced neurogenesis and synaptogenesis have been implicated as features of DS development. Yet, what and how specific neurons and synaptic contacts are affected at which period of development and what molecular pathways underlie these defects that lead to intellectual disability remain unclear. The parent award was funded to build models based on human induced pluripotent stem cells (iPSCs), to interrogate how T21 disrupts developmental processes in DS. The iPSC model will be validated by integrating cellular changes and molecular signatures of single cells in vitro with DS prenatal cortex. The parent award relies on maintenance, differentiation and analysis of iPSC derived neurons in vitro for two of the three Aims. This supplement requests funding for cell culture related equipment that is required to carry out Aims 2 and 3 of the parent award. Funding is requested to replace two cell culture incubators for maintenance of iPSCs and differentiated neurons in Aim 2 and 3. Funding is also requested for an additional electrophysiological rig for analysis of iPSC derived neurons in Aim 3. The parent award included minimal equipment funding and these costs were unforeseen when the application was awarded.

摘要