Linen Savannah R, Chang Nelson H, Hess Ellen J, Stanley Garrett B, Waiblinger Christian
Program in Bioinformatics, Georgia Institute of Technology, Atlanta, GA, USA.
Wallace H Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, USA.
bioRxiv. 2025 Jan 29:2024.06.05.597339. doi: 10.1101/2024.06.05.597339.
Parkinson's disease (PD) is characterized by the degeneration of dopaminergic (DA) neurons in the substantia nigra pars compacta, leading to dopamine depletion in the striatum and the hallmark motor symptoms of the disease. However, non-motor deficits, particularly sensory symptoms, often precede motor manifestations, offering a potential early diagnostic window. The impact of non-motor deficits on sensation behavior and the underlying mechanisms remain poorly understood. In this study, we examined changes in tactile sensation within a parkinsonian state by employing a mouse model of PD induced by 6-hydroxydopamine (6-OHDA) to deplete striatal DA. Leveraging the conserved mouse whisker system as a model for tactile-sensory stimulation, we conducted psychophysical experiments to assess sensory-driven behavioral performance during a tactile detection task in both the healthy and PD-like state. Our findings reveal a range of deficits across subjects following 6-OHDA lesion, including DA loss, motor asymmetry, weight loss, and varying levels of altered tactile sensation behavior. Behavioral changes ranged from no impairments in minor cases to isolated sensory-behavioral deficits in moderate cases and severe motor dysfunction in advanced stages. These results underscore the complex relationship between DA imbalance and sensory-motor processing, emphasizing the need for precise and multifaceted behavioral measurements to accurately capture the diverse manifestations of PD.
帕金森病（PD）的特征是黑质致密部多巴胺能（DA）神经元变性，导致纹状体多巴胺耗竭及该疾病典型的运动症状。然而，非运动缺陷，尤其是感觉症状，往往先于运动表现出现，提供了一个潜在的早期诊断窗口。非运动缺陷对感觉行为的影响及其潜在机制仍知之甚少。在本研究中，我们通过使用6-羟基多巴胺（6-OHDA）诱导的帕金森病小鼠模型来耗尽纹状体多巴胺，研究帕金森状态下触觉感觉的变化。利用保守的小鼠触须系统作为触觉感觉刺激模型，我们进行了心理物理学实验，以评估健康状态和类帕金森状态下触觉检测任务中感觉驱动的行为表现。我们的研究结果显示，6-OHDA损伤后各受试者存在一系列缺陷，包括多巴胺丧失、运动不对称、体重减轻以及不同程度的触觉感觉行为改变。行为变化范围从轻微病例无损伤到中度病例孤立的感觉行为缺陷，再到晚期严重的运动功能障碍。这些结果强调了多巴胺失衡与感觉运动处理之间的复杂关系，强调需要进行精确和多方面的行为测量，以准确捕捉帕金森病的各种表现。
