Richter A, Brotchie J M, Crossman A R, Löscher W
Department of Pharmacology, Toxicology and Pharmacy, School of Veterinary Medicine, Hannover, Germany.
Mov Disord. 1998 Jul;13(4):718-25. doi: 10.1002/mds.870130419.
The genetically dystonic (dtSZ) hamster, an animal model of idiopathic paroxysmal dystonia, displays attacks of generalized twisting movements and abnormal postures of limbs and trunk either spontaneously or in response to mild stress. This experimental model may be helpful to give insights into the pathophysiology of idiopathic dystonia in man. In the present study, the regional uptake of [3H]-2-deoxyglucose (2-DG) was examined in brains (75 brain regions) of dtSZ hamsters during the expression of severe dystonia. 2-DG autoradiography revealed significant changes of 2-DG uptake in discrete brain regions of dtSZ hamsters compared with age-matched, nondystonic control hamsters. In dystonic hamsters, a dramatic increase of 2-DG uptake was observed in the red nucleus (159% over control). Furthermore, enhanced 2-DG uptake was found in the ventromedial, ventrolateral, and anteroventral nuclei of the thalamus (19-42%) and in the medial vestibular nucleus (23%). A significant decrease in 2-DG uptake in deep cerebellar nuclei (-30%) may be the result of decreased synaptic activity of GABAergic neurons within these structures resulting in enhanced excitatory output to red nucleus, thalamic, and vestibular nuclei. In dtSZ hamsters, the 2-DG uptake was not significantly altered overall within the basal ganglia. Significant increases of 14% were, however, found in discrete parts of the caudate putamen in which recent studies revealed changes of dopamine receptors. Altered neural activity within the basal ganglia may therefore contribute to increased 2-DG uptake in the ventral thalamic nuclei as well as to decreased 2-DG uptake (-13%) found in the reticular thalamic nucleus. Although the present data are in line with the concept that abnormal thalamocortical activity seems to be critically involved in the dystonic syndrome, altered activities in other motor areas than output structures of the basal ganglia, such as in the red nucleus, may contribute to clinical manifestation of dystonia in mutant hamsters.
遗传性肌张力障碍（dtSZ）仓鼠是特发性阵发性肌张力障碍的动物模型，其会自发地或在轻度应激反应下出现全身性扭转运动发作以及四肢和躯干的异常姿势。该实验模型可能有助于深入了解人类特发性肌张力障碍的病理生理学。在本研究中，在严重肌张力障碍发作期间，对dtSZ仓鼠的大脑（75个脑区）中[3H]-2-脱氧葡萄糖（2-DG）的区域摄取情况进行了检测。2-DG放射自显影显示，与年龄匹配的非肌张力障碍对照仓鼠相比，dtSZ仓鼠的离散脑区中2-DG摄取有显著变化。在肌张力障碍仓鼠中，红核中的2-DG摄取显著增加（比对照高159%）。此外，丘脑腹内侧核、腹外侧核和前腹侧核中的2-DG摄取增强（19%-42%），内侧前庭核中的2-DG摄取也增强（23%）。小脑深部核团中2-DG摄取显著减少（-30%），这可能是这些结构内GABA能神经元突触活动减少的结果，从而导致对红核、丘脑核和前庭核的兴奋性输出增强。在dtSZ仓鼠中，基底神经节内的2-DG摄取总体上没有显著改变。然而，在尾状壳核的离散部分发现有14%的显著增加，最近的研究显示这些部位的多巴胺受体有变化。因此，基底神经节内神经活动的改变可能导致腹侧丘脑核中2-DG摄取增加，以及网状丘脑核中2-DG摄取减少（-13%）。尽管目前的数据符合异常丘脑皮质活动似乎在肌张力障碍综合征中起关键作用这一概念，但基底神经节输出结构以外的其他运动区域（如红核）的活动改变可能也有助于突变仓鼠肌张力障碍的临床表现。
