Andersen Anders H, Hardy Peter A, Forman Eric, Gerhardt Greg A, Gash Don M, Grondin Richard C, Zhang Zhiming
Department of Anatomy and Neurobiology, Chandler Medical Center, University of Kentucky, Lexington, KY, USA; Magnetic Resonance Imaging and Spectroscopy Center, University of Kentucky, Lexington, KY, USA.
Department of Anatomy and Neurobiology, Chandler Medical Center, University of Kentucky, Lexington, KY, USA.
Neurobiol Aging. 2015 Feb;36(2):1174-82. doi: 10.1016/j.neurobiolaging.2014.10.014. Epub 2014 Oct 16.
The prevalence of both parkinsonian signs and Parkinson's disease (PD) per se increases with age. Although the pathophysiology of PD has been studied extensively, less is known about the functional changes taking place in the basal ganglia circuitry with age. To specifically address this issue, 3 groups of rhesus macaques were studied: normal middle-aged animals (used as controls), middle-aged animals with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism, and aged animals (>20 years old) with declines in motor function. All animals underwent the same behavioral and pharmacologic magnetic resonance imaging (phMRI) procedures to measure changes in basal ganglia function in response to dopaminergic drug challenges consisting of apomorphine administration followed by either a D1 (SCH23390) or a D2 (raclopride) receptor antagonist. Significant functional changes were predominantly seen in the external segment of the globus pallidus (GPe) in aged animals and in the striatum (caudate nucleus and putamen) in MPTP-lesioned animals. Despite significant differences seen in the putamen and GPe between MPTP-lesioned versus aged animals, a similar response profile to dopaminergic stimulations was found between these 2 groups in the internal segment of the GP. In contrast, the pharmacologic responses seen in the control animals were much milder compared with the other 2 groups in all the examined areas. Our phMRI findings in MPTP-lesioned parkinsonian and aged animals suggest that changes in basal ganglia function in the elderly may differ from those seen in parkinsonian patients and that phMRI could be used to distinguish PD from other age-associated functional alterations in the brain.
帕金森氏症体征和帕金森病（PD）本身的患病率均随年龄增长而增加。尽管对PD的病理生理学已进行了广泛研究，但关于基底神经节回路随年龄发生的功能变化却知之甚少。为了专门解决这个问题，我们研究了3组恒河猴：正常中年动物（用作对照）、用1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）诱发帕金森症的中年动物以及运动功能下降的老年动物（>20岁）。所有动物都接受了相同的行为和药物磁共振成像（phMRI）程序，以测量基底神经节功能在多巴胺能药物激发下的变化，激发过程包括给予阿扑吗啡，随后给予D1（SCH23390）或D2（雷氯必利）受体拮抗剂。在老年动物的苍白球外部段（GPe）和MPTP损伤动物的纹状体（尾状核和壳核）中主要观察到了显著的功能变化。尽管在MPTP损伤动物与老年动物之间的壳核和GPe中观察到了显著差异，但在苍白球内部段的这两组动物中发现了对多巴胺能刺激的相似反应模式。相比之下，在所有检查区域中，对照动物的药物反应与其他两组相比要温和得多。我们在MPTP损伤的帕金森病动物和老年动物中的phMRI结果表明，老年人基底神经节功能的变化可能与帕金森病患者不同，并且phMRI可用于区分PD与大脑中其他与年龄相关的功能改变。
