Regensburger Martin, Kohl Zacharias, Grundmann Kathrin, Winner Beate, Riess Olaf, Winkler Jürgen
Department of Neurology, University of Regensburg, Regensburg, Germany.
Neuroreport. 2009 Nov 25;20(17):1529-33. doi: 10.1097/WNR.0b013e328331c761.
Hereditary dystonias in humans are frequently related to a specific mutation of the DYT1 gene that encodes torsinA. This mutation has been shown to disrupt neuronal cell migration during development. We compared adult neurogenesis, occurring in the hippocampus and the olfactory bulb, in transgenic mice overexpressing either the wild-type or mutant form of human torsinA. Neurogenesis was assessed by quantification of bromodeoxyuridine-labeled cells. Both transgenic mouse models displayed perinuclear inclusions in the brainstem and in mitral cells of the olfactory bulb, altered striatal dopamine levels, and behavioral abnormalities. However, both hippocampal and olfactory neurogenesis levels were unchanged compared with control animals. We conclude that overexpression of human wild-type or mutant torsinA does not affect the survival of adult newborn neurons.
人类遗传性肌张力障碍常与编码扭转蛋白A的DYT1基因的特定突变有关。该突变已被证明会破坏发育过程中的神经元细胞迁移。我们比较了在海马体和嗅球中发生的成年神经发生情况,这些实验对象是过表达野生型或突变型人类扭转蛋白A的转基因小鼠。通过对溴脱氧尿苷标记的细胞进行定量来评估神经发生。两种转基因小鼠模型在脑干和嗅球的二尖瓣细胞中均显示核周包涵体,纹状体多巴胺水平改变,以及行为异常。然而,与对照动物相比,海马体和嗅觉神经发生水平均未改变。我们得出结论,人类野生型或突变型扭转蛋白A的过表达不会影响成年新生神经元的存活。