Vocalization deficits in parkinson rats: Does L-DOPA harm or help therapy?

描述(申请人提供)：这项研究的长期目标是探索复杂的感觉运动丰富(运动)和药物对早期帕金森病(PD)大鼠模型的感觉运动功能的治疗效果，作为一种翻译方法，以加速对人类PD治疗的影响。尽管在人类和动物模型中都有行为和神经化学证据，但帕金森病患者很少在确诊后立即进行运动/感觉运动康复。因此，失去了保护剩余的活性多巴胺神经元和减缓运动症状进展的机会。一旦确诊，干预的主要形式是引入药物治疗，主要是左旋多巴。然而，在帕金森病的早期阶段，左旋多巴的应用是有争议的。此外，左旋多巴对早期运动的潜在益处的影响尚不清楚。这项应用反映了一项独特的研究，旨在解决早期运动的治疗效果，并在动物模型中检查多巴胺增强药物对言语和发声(发声)功能结果的作用。早期帕金森病大鼠模型将被用来测试多巴胺耗竭对超声发声(大鼠声音/言语感觉运动控制的模拟)的影响。大鼠将在对照条件下、神经毒素暴露后立即(PD模型)以及在使用和不使用左旋多巴的发声训练(治疗)后进行测试。将测量大鼠超声发声声学参数和多巴胺储备的变化，作为运动或药物治疗后疾病严重程度和功能改善的指标。相关性：这项研究将加速获得所需的神经生物学和行为学证据，以说服临床和基础科学界相信早期重复感觉运动丰富以减缓人类帕金森病疾病进展的合法治疗价值。此外，它将提供一个基础，将导致在动物模型中对左旋多巴在运动和不运动情况下的效果进行良好的对照研究。这将创建一个翻译模型，用于解决人类早期服用多巴胺增强药物的益处/混淆问题。通俗易懂的研究问题：运动(发声疗法)是否延缓了早期帕金森病的进展，并改善了整体功能结果？抗帕金森病药物对这一过程有帮助还是有干扰作用？

DESCRIPTION (provided by applicant): The long-term objective of this research is to explore the therapeutic effects of complex sensorimotor enrichment (exercise) and medication on sensorimotor function in a rat model of early Parkinson's disease (PD) as a translational approach to accelerate the impact for treatment in human PD. Despite the behavioral and neurochemical evidence in both human and animal models, people with PD are rarely referred to exercise/sensorimotor rehabilitation immediately upon diagnosis. As a result, the opportunity to protect the remaining viable dopamine neurons and slow the progression of motor symptoms is lost. Upon diagnosis, the primary form of intervention is the introduction of pharmacotherapy, primarily levodopa. However, in the early stages of PD, administration of levodopa is controversial. Further, the effects of levodopa on the potential benefits of early exercise are unknown. This application reflects a unique study to address the therapeutic effects of early exercise and to examine the role of dopamine-augmenting drugs on functional outcomes in speech and voice (vocalization) in an animal model. A rat model of early PD will be employed to test the effects of dopamine depletion on Ultrasonic Vocalization (rat analogue of voice/speech sensorimotor control). Rats will be tested in a control condition, immediately after neurotoxin exposure (PD model), and after vocal exercise (therapy) with and without levodopa. Changes in rat Ultrasonic Vocalization acoustic parameters and dopamine sparing will be measured as an index of disease severity and functional improvement after exercise or pharmacological treatment. Relevance: This research is will accelerate the acquisition of the neurobiological and behavioral evidence needed to convince both clinical and basic science communities of the legitimate therapeutic value of early repetitive sensorimotor enrichment to slow disease progression in human PD. Further, it is to provide a foundation that will lead to a well-controlled study of the effects of levodopa with and without exercise in an animal model. This will create a translational model for addressing benefits/confounds in early administration of dopamine-augmenting medications in humans. Plain-Language Research Questions: Does exercise (voice therapy) slow the progression of early Parkinson Disease and improve overall functional outcomes? Do anti-Parkinson medications help or interfere with this process?