DSU Sub-Project 1

黑质致密部（SNc）是一种调节自主运动控制的结构，SNc中多巴胺能神经元的死亡导致许多与帕金森病（PD）相关的经典运动缺陷。大多数常规治疗可以缓解症状，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治疗可以替代丢失的细胞，但对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，因为移植的大多数细胞无法存活。阐明调节多巴胺神经发育的因素可能会导致新的治疗方法或增加PD替代疗法的有效性。在大鼠大脑中，孕激素受体（PRs）在围产期SNc中短暂表达，表明该激素在该区域的发育中起作用。Mennella博士建议表征小鼠黑质中黄体酮受体的时间表达模式，并确定它们在该区域的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，以及更多未成熟的SNc多巴胺投射的主要受体海马和成年后更大的运动缺陷。

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.