Motor System Development in the Absence of Cell Death

在没有细胞死亡的情况下运动系统的发育

• 批准号: 7234347
• 负责人: RONALD W OPPENHEIM
• 金额: $ 34.33万
• 依托单位: WAKE FOREST UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-06-01 至 2009-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7234347
• 关键词: Motor; System; Development; Absence; Cell; Motor; System; Development; Absence; Cell

DESCRIPTION (provided by applicant): The major objective of the proposed research is to examine the development of the neuromuscular system in a mouse model in which programmed cell death (PCD) of motoneurons has been eliminated by genetic deletion of pro-apoptotic genes. The use of this model will allow us to address issues of basic biology such as the adaptive significance of PCD in the nervous system and whether excess neurons can be functionally incorporated into the developing nervous system. Neuroanatomical, physiological and behavioural methods will be employed to examine both spinal and cranial motoneurons. We well determine whether rescued neurons differentiate normally; and whether physiological and behavioural assays of neuromuscular function are affected by the presence of tens of thousands of rescued motoneurons. Additionally, we plan to take advantage of the fact that even following injury, motoneurons in these mice can survive. Accordingly, we will cross these mice with a mouse model of Amyotrophic Lateral Sclerosis (ALS), the SOD1 mutant, and determine whether the pathological signs of motoneuron disease are ameliorated. In both the developmental and SOD1 studies, treatment with neurotrophic factors (NTFs) will be used in an attempt to optimize the development and maintenance of the neuromuscular system. The use of mice lacking motoneuron cell death provides a unique opportunity to examine: (1) the widely accepted but largely untested assumption that the PCD of neurons during development subserves essential adaptive functions that if perturbed would result in neurobehavioral dysfunction; and (2) the role of PCD and neurotrophic factors in a mouse model of ALS.

描述（由申请人提供）：拟议研究的主要目的是检查小鼠模型中神经肌肉系统的发展，在小鼠模型中，通过促凋亡基因的遗传缺失，已经消除了运动神经元的编程细胞死亡（PCD）。这种模型的使用将使我们能够解决基本生物学问题，例如PCD在神经系统中的适应性意义，以及是否可以将多余的神经元纳入发展中的神经系统。将采用神经解剖学，生理和行为方法检查脊柱和颅运动神经元。我们很好地确定救出神经元是否正常区分；神经肌肉功能的生理和行为测定是否受到成千上万的救出运动神经元的存在。此外，我们计划利用这样一个事实，即即使受伤，这些小鼠中的运动神经元也可以生存。因此，我们将与肌萎缩性侧索硬化症（ALS），SOD1突变体的小鼠模型越过这些小鼠，并确定是否改善了运动神经元疾病的病理迹象。在发育和SOD1研究中，将使用神经营养因子（NTF）的治疗来优化神经肌肉系统的发展和维持。缺乏运动神经元细胞死亡的小鼠提供了一个独特的机会来检查：（1）开发过程中神经元的PCD的广泛接受的假设，即如果扰动会导致神经行为功能障碍，则神经元的PCD基本自适应功能； （2）PCD和神经营养因子在ALS小鼠模型中的作用。