Kordys Elena, Apetz Nadine, Schneider Katharina, Duncan Eilidh, Büschbell Beatriz, Rohleder Cathrin, Sué Michael, Drzezga Alexander, Neumaier Bernd, Timmermann Lars, Endepols Heike
Institute of Radiochemistry and Experimental Molecular Imaging, University Hospital of Cologne, Kerpener Str. 62, 50937, Köln, Germany.
Department of Neurology, University Hospital of Cologne, Kerpener Str. 62, 50937, Köln, Germany.
EJNMMI Res. 2017 Aug 23;7(1):68. doi: 10.1186/s13550-017-0317-9.
In Parkinson's disease (PD), cerebral dopamine depletion is associated with PD subtype-specific metabolic patterns of hypo- and hypermetabolism. It has been hypothesised that hypometabolism reflects impairment, while hypermetabolism may indicate compensatory activity. In order to associate metabolic patterns with pathophysiological and compensatory mechanisms, we combined resting state [F]FDG-PET (to demonstrate brain metabolism in awake animals), [F]FDOPA-PET (dopamine depletion severity) and gait analysis in a unilateral 6-hydroxydopamine rat model.
We found unilateral nigro-striatal dopaminergic loss to decrease swing speed of the contralesional forelimb and stride length of all paws in association with depletion severity. Depletion severity was found to correlate with compensatory changes such as increased stance time of the other three paws and diagonal weight shift to the ipsilesional hind paw. [F]FDG-PET revealed ipsilesional hypo- and contralesional hypermetabolism; metabolic deactivation of the ipsilesional network needed for sensorimotor integration (hippocampus/retrosplenial cortex/lateral posterior thalamus) was solely associated with bradykinesia, but hypometabolism of the ipsilesional rostral forelimb area was related to both pathological and compensatory gait changes. Mixed effects were also found for hypermetabolism of the contralesional midbrain locomotor region, while contralesional striatal hyperactivation was linked to motor impairments rather than compensation.
Our results indicate that ipsilesional hypo- and contralesional hypermetabolism contribute to both motor impairment and compensation. This is the first time when energy metabolism, dopamine depletion and gait analysis were combined in a hemiparkinsonian model. By experimentally increasing or decreasing compensational brain activity, its potential and limits can be further investigated.
在帕金森病（PD）中，脑内多巴胺耗竭与PD亚型特异性的代谢减低和代谢亢进模式相关。据推测，代谢减低反映功能受损，而代谢亢进可能表明存在代偿性活动。为了将代谢模式与病理生理和代偿机制联系起来，我们在单侧6-羟基多巴胺大鼠模型中结合了静息态[F]FDG-PET（用于显示清醒动物的脑代谢）、[F]FDOPA-PET（多巴胺耗竭严重程度）和步态分析。
我们发现单侧黑质-纹状体多巴胺能缺失会降低对侧前肢的摆动速度以及所有爪子的步幅长度，且与耗竭严重程度相关。发现耗竭严重程度与代偿性变化相关，如其他三只爪子的站立时间增加以及对角重量转移至同侧后爪。[F]FDG-PET显示同侧代谢减低和对侧代谢亢进；感觉运动整合所需的同侧网络（海马体/ retrosplenial皮质/外侧后丘脑）的代谢失活仅与运动迟缓相关，但同侧喙部前肢区域的代谢减低与病理和代偿性步态变化均有关。对侧中脑运动区域的代谢亢进也发现有混合效应，而对侧纹状体的过度激活与运动障碍而非代偿相关。
我们的结果表明同侧代谢减低和对侧代谢亢进均导致运动障碍和代偿。这是首次在偏侧帕金森病模型中将能量代谢、多巴胺耗竭和步态分析结合起来。通过实验性地增加或减少代偿性脑活动，可以进一步研究其潜力和局限性。
