...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>The European Journal of Neuroscience >Age-related decline in striatal dopamine content and motor performance occurs in the absence of nigral cell loss in a genetic mouse model of Parkinson's disease.
【24h】

Age-related decline in striatal dopamine content and motor performance occurs in the absence of nigral cell loss in a genetic mouse model of Parkinson's disease.

机译：在帕金森氏病的遗传小鼠模型中，在没有黑质细胞丢失的情况下，纹状体多巴胺含量和运动能力的下降与年龄有关。

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Dopamine cytotoxicity is thought to contribute towards the selective loss of substantia nigra pars compacta dopamine neurons and disease progression in Parkinson's disease. However, the long-term toxicity of dopamine in vivo has not previously been established. The vesicular monoamine transporter 2 (VMAT2) sequesters monoamines into synaptic vesicles, a process that, in addition to being important in normal transmission, may also act to keep intracellular levels of monoamine neurotransmitters below potentially toxic thresholds. The homozygous VMAT2-hypomorphic mouse has an insertion in the VMAT2 gene (Slc18a2). Consequently, VMAT2-deficient mice (VD(-/-)) have an approximately 95% reduction in VMAT2 expression and an equivalent level of dopamine depletion in the striatum which results in moderate motor impairment. Here, we show that L-DOPA induces locomotor hyperactivity in VD(-/-) mice and reverses the deficit in motor coordination and balance as tested with the rotarod. We report that evidence for cytosolic accumulation of dopamine in substantia nigra neurons in these mice is two-fold: firstly, there is reduced phosphorylation of tyrosine hydroxylase at the residue associated with catechol feedback inhibition; and, secondly, there are increased rates of dopamine turnover at 6, 12 and 24 months of age. These animals exhibit a progressive decline in striatal monoamine levels and rotarod performance with increasing age. However, despite these data, there was no loss of nigral dopamine neurons as estimated by quantification of tyrosine hydroxylase-immunoreactive cells in the substantia nigra pars compacta of old VD(-/-) mice (24-month-old), implying that these age-dependent manifestations may be due to senescence alone.
机译：多巴胺的细胞毒性被认为有助于黑质致密性多巴胺神经元的选择性丢失和帕金森氏病的疾病进展。但是，多巴胺在体内的长期毒性尚未建立。囊泡单胺转运蛋白2（VMAT2）将单胺螯合到突触小泡中，这一过程除了在正常传播中很重要外，还可以使细胞内单胺神经递质的水平保持在潜在毒性阈值以下。纯合的VMAT2亚型小鼠在VMAT2基因（Slc18a2）中插入。因此，VMAT2缺陷小鼠（VD（-/-））的纹状体中VMAT2表达降低了约95％，多巴胺水平降低了，从而导致了中等程度的运动障碍。在这里，我们显示L-DOPA在VD（-/-）小鼠中诱导运动亢进并逆转了用旋转脚架测试的运动协调和平衡不足。我们报道，在这些小鼠中黑质黑质神经元中多巴胺的胞质蓄积证据是两方面的：首先，酪氨酸羟化酶的磷酸化减少与邻苯二酚反馈抑制有关的残基;其次，在6、12和24个月大时，多巴胺周转率增加。这些动物随着年龄的增长，纹状体单胺水平和轮状动物的表现逐渐下降。但是，尽管有这些数据，但通过定量分析老的VD（-/-）小鼠（24个月大）黑质致密部中酪氨酸羟化酶免疫反应性细胞所估计的黑质多巴胺神经元没有丢失，这表明这些年龄依赖性的表现可能仅由于衰老。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号