Raike Robert S, Hess Ellen J, Jinnah H A
Emory University School of Medicine, Department of Pharmacology, Woodruff Memorial Research Building, 101 Woodruff Circle, Atlanta, GA 30322, United States.
Emory University School of Medicine, Department of Pharmacology, Woodruff Memorial Research Building, 101 Woodruff Circle, Atlanta, GA 30322, United States; Emory University School of Medicine, Department of Neurology, Woodruff Memorial Research Building, 101 Woodruff Circle, Atlanta, GA 30322, United States.
Brain Res. 2015 Jun 22;1611:56-64. doi: 10.1016/j.brainres.2015.03.011. Epub 2015 Mar 16.
Cerebellar degeneration is traditionally associated with ataxia. Yet, there are examples of both ataxia and dystonia occurring in individuals with cerebellar degeneration. There is also substantial evidence suggesting that cerebellar dysfunction alone may cause dystonia. The types of cerebellar defects that may cause ataxia, dystonia, or both have not been delineated. In the current study, we explored the relationship between cerebellar degeneration and dystonia using the leaner mouse mutant. Leaner mice have severe dystonia that is associated with dysfunctional and degenerating cerebellar Purkinje cells. Whereas the density of Purkinje cells was not significantly reduced in 4 week-old leaner mice, approximately 50% of the neurons was lost by 34 weeks of age. On the other hand, the dystonia and associated functional disability became significantly less severe during this same interval. In other words, dystonia improved as Purkinje cells were lost, suggesting that dysfunctional Purkinje cells, rather than Purkinje cell loss, contribute to the dystonia. These results provide evidence that distorted cerebellar function may cause dystonia and support the concept that different types of cerebellar defects can have different functional consequences.
传统上，小脑变性与共济失调相关。然而，在小脑变性患者中既有共济失调的例子，也有肌张力障碍的例子。也有大量证据表明，仅小脑功能障碍就可能导致肌张力障碍。可能导致共济失调、肌张力障碍或两者皆有的小脑缺陷类型尚未明确。在当前的研究中，我们使用瘦素小鼠突变体来探索小脑变性与肌张力障碍之间的关系。瘦素小鼠有严重的肌张力障碍，这与功能失调和退化的小脑浦肯野细胞有关。在4周龄的瘦素小鼠中，浦肯野细胞的密度没有显著降低，但到34周龄时，约50%的神经元丢失。另一方面，在同一时期，肌张力障碍和相关的功能残疾变得明显不那么严重。换句话说，随着浦肯野细胞的丢失，肌张力障碍有所改善，这表明功能失调的浦肯野细胞而非浦肯野细胞的丢失导致了肌张力障碍。这些结果提供了证据，证明小脑功能紊乱可能导致肌张力障碍，并支持不同类型的小脑缺陷可能产生不同功能后果的观点。
