Pharmacologic MRI (phMRI) as a tool to differentiate Parkinson's disease-related from age-related changes in basal ganglia function.
Pharmacologic MRI (phMRI) as a tool to differentiate Parkinson's disease-related from age-related changes in basal ganglia function.
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DOI：
10.1016/j.neurobiolaging.2014.10.014
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发表时间：
2015-02
影响因子：
4.2
通讯作者：
Zhang Z
中科院分区：
文献类型：
--
作者：
Andersen AH;Hardy PA;Forman E;Gerhardt GA;Gash DM;Grondin RC;Zhang Z
帕金森综合征和帕金森病（PD）本身的患病率随着年龄的增长而增加。虽然PD的病理生理学已被广泛研究，但对基底神经节回路随年龄变化的功能变化知之甚少。为了具体解决这个问题，研究了三组恒河猴：正常中年动物（用作对照），患有MPTP诱导的帕金森症的中年动物和运动功能下降的老年动物（>20岁）。所有动物均接受相同的行为和phMRI程序，以测量基底神经节功能对多巴胺能药物激发的反应变化，所述多巴胺能药物激发包括阿朴吗啡（APO）给药，然后是D1（SCH 23390）或D2（雷氯必利）受体拮抗剂。显着的功能变化主要见于老年动物的苍白球（GPe）的外部部分和MPTP损伤动物的纹状体（尾状核和壳核）。尽管在MPTP损伤与老年动物之间的壳核和GPe中观察到显著差异，但在苍白球（GPi）的内部段中发现这两组之间对多巴胺能刺激的反应特征相似。相比之下，在所有检查区域，对照组动物中观察到的药理学反应比其他两组轻得多。我们在MPTP损伤的帕金森病和老年动物中的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的变化不同，phMRI可用于区分PD与其他年龄相关的脑功能改变。
The prevalence of both parkinsonian signs and Parkinson's disease (PD) per se increases with age. While 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, three groups of rhesus macaques were studied: Normal middle-aged animals (used as controls), middle-aged animals with MPTP-induced parkinsonism, and aged animals (>20 years old) with declines in motor function. All animals underwent the same behavioral and phMRI procedures to measure changes in basal ganglia function in response to dopaminergic drug challenges consisting of apomorphine (APO) administration followed by either a D1 (SCH23390) or 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 two groups in the internal segment of the globus pallidus (GPi). In contrast, the pharmacological responses seen in the control animals were much milder compared with the other two groups in all 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.