UDEL Subproject 1

UDEL子项目1

基本信息

批准号：
8727229
负责人：
ANNA Y KLINTSOVA
金额：
$ 17.47万
依托单位：
DELAWARE STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/8727229
关键词：
Adult Androgens Animals Attention Brain Brain region Cell Survival Cells Centers of Research Excellence Cessation of life Corpus striatum structure Data Delaware Development Developmental Process Diffuse Disease Dopamine Dopaminergic Cell Effectiveness Estrogens Exposure to Face Female Fetal Tissues Hormones Human In Vitro Knock-out Knockout Mice Knowledge Lead Mediating Midbrain structure Molecular Motor Movement Disorders Mus Neurons Neurosciences Research Parkinson Disease Pattern Perinatal Pharmaceutical Preparations Pharmacotherapy Phenotype Predisposition Prevention Production Progesterone Progesterone Receptors Rattus Replacement Therapy Role Specificity Structure Substantia nigra structure Symptoms Task Performances Testosterone Time Tissues Transgenic Mice Transplantation Transplanted tissue Treatment Effectiveness age related brain cell conventional therapy dopaminergic neuron fetal innovation male migration motor control motor deficit nerve stem cell neurodevelopment neuron development neuron loss nigrostriatal system novel novel strategies pars compacta postnatal prevent receptor expression research study stem cell therapy steroid hormone ward

项目摘要

The substantia nigra, pars compacta (SNc) is a structure that modulates voluntary motor control, and the death of the dopaminergic neurons in the SNc leads to many of the classic motor deficits associated with the Parkinson's disease (PD). Most conventional treatments alleviate symptoms but do not prevent the eventual death of neurons in the SNc. While fetal tissue transplant and stem cell therapy serve to replace lost cells, incomplete knowledge on dopamine neuron development within the SNc has limited the effectiveness of these treatments as most cells in the transplant fail to survive. Elucidating the factors that modulate dopamine neural development could lead to novel treatment approaches or increase the effectiveness of these replacement therapies in PD. In the rat brain, progesterone receptors (PRs) are expressed transiently in the perinatal SNc, suggesting a role for this hormone in the development of this region. Dr. Mennella proposes to characterize the temporal expression pattern of progesterone receptors in the mouse substantia nigra and determine their roles in the morphological and phenotypic development of that region. She also proposes to use PR knock-out (PRKO) mice to determine if absence of PRs during development leads to greater dopaminergic cell loss in the adult SNc, and more immature projections into the straitum, the primary recipient of SNc dopamine projections and greater motor deficits in adulthood.

黑质致密部 (SNc) 是调节自主运动控制的结构，SNc 中多巴胺能神经元的死亡会导致许多与帕金森病 (PD) 相关的经典运动缺陷。大多数传统治疗可以缓解症状，但不能阻止 SNc 神经元的最终死亡。虽然胎儿组织移植和干细胞疗法可以替代丢失的细胞，但由于移植物中的大多数细胞无法存活，对 SNc 内多巴胺神经元发育的不完整了解限制了这些治疗的有效性。阐明调节多巴胺神经发育的因素可能会带来新的治疗方法或提高这些替代疗法在帕金森病中的有效性。在大鼠大脑中，黄体酮受体 (PR) 在围产期 SNc 中短暂表达，表明该激素在该区域的发育中发挥作用。 Mennella 博士建议表征小鼠黑质中孕酮受体的时间表达模式，并确定它们在该区域形态和表型发育中的作用。她还建议使用 PR 敲除 (PRKO) 小鼠来确定发育过程中 PR 的缺失是否会导致成年 SNc 中更多的多巴胺能细胞损失，以及更多不成熟的投射进入纹层（SNc 多巴胺投射的主要接受者）和更大的运动能力。成年后的缺陷。