Effects of cholinergic axonal plasticity on spatial orientation

项目总结/摘要 神经退行性疾病可对患者维持空间神经元的能力产生显著损害。 导向美国人口目前不断变化的年龄结构，加上缺乏有效的 神经退行性疾病的治疗给社会带来了严重的挑战， 这些病人。评估神经退行性疾病的新疗法将取决于确定一种新的治疗方法。 合适的空间定向动物模型。老鼠和人类一样，利用环境和自我运动的线索 以保持空间方向。我的研究集中在为老鼠开发任务， 任何信息来源。基底前脑胆碱能投射明显变性 在老年痴呆症的发展过程中。本提案中概述的实验 代表了研究增强神经可塑性以改善认知缺陷的潜力的下一步 与基底前脑胆碱能神经元的病理学相关。该提案的一个目标是审查 抗Nogo-A免疫疗法是否足以促进基底前脑胆碱能神经可塑性 成年和衰老大鼠的神经元。另一个目标是评估增强神经可塑性的程度， 任何一个年龄都足以改善自我运动线索处理缺陷。最后一个目标是提供培训 为本科生和研究生的经验，将建立一个基础，以追求职业生涯中， 生物医学科学这些研究的结果将促进我们对衰老对人的影响的理解。 空间定位和评估抗Nogo-A免疫疗法作为一种新的干预措施的潜力， 神经退行性疾病

Project Summary/Abstract Neurodegenerative disorders can produce significant impairments in a patient’s ability to maintain spatial orientation. The current changing age structure of the US population in combination with lack of effective treatments for neurodegenerative disorders presents serious challenges for society in the management of these patients. Evaluating novel therapies for neurodegenerative disorders will depend on identifying an appropriate animal model of spatial orientation. Rats, like humans, use environmental and self-movement cues to maintain spatial orientation. My research has focused on developing tasks for rats that dissociate the use of either source of information. The basal forebrain cholinergic projections undergoes significant degeneration during the progression of Dementia of the Alzheimer's Type. The experiments outlined in this proposal represent the next step in investigating the potential of enhancing neuroplasticity to improve cognitive deficits associated with pathology in the basal forebrain cholinergic neurons. One goal of the proposal examines whether anti-Nogo-A immunotherapy is sufficient to promote neuroplasticity basal forebrain cholinergic neurons in adult and senescent rats. Another goal is to evaluate the extent that enhanced neuroplasticity at either age is sufficient to ameliorate self-movement cue processing deficits. A final goal is to provide training experiences for undergrad and graduate students that will establish a foundation to pursue a career in the biomedical sciences. The results of these studies will advance our understanding of the effects of aging on spatial orientation and evaluate the potential of anti-Nogo-A immunotherapies as a novel intervention for neurodegenerative disorders.