Climbing fiber-Purkinje cell synaptic pathology in tremor and cerebellar degenerative diseases
Climbing fiber-Purkinje cell synaptic pathology in tremor and cerebellar degenerative diseases
复制标题
DOI：
10.1007/s00401-016-1626-1
复制
发表时间：
2017-01-01
影响因子：
12.7
通讯作者：
Faust, Phyllis L.
中科院分区：
文献类型：
--
作者：
Kuo, Sheng-Han;Lin, Chi-Ying;Faust, Phyllis L.
特发性震颤（ET）患者小脑中存在爬纤维-浦肯野细胞（CF-PC）突触连接的改变，这些改变与震颤的严重程度相关。这些死后变化是否是ET特有的仍有待研究。我们评估了一系列退行性运动障碍[10例帕金森病（PD）病例，10例多系统萎缩（MSA）病例，10例脊髓小脑共济失调1型（SCA 1）病例和20例ET病例]和25例对照的死后小脑CF-PC突触病理学。我们观察到这些疾病之间CF病理特征的差异。PD组和ET组均有较多的CFs延伸到平行纤维（PF）区，但ET组PF区CFs分支较PD组复杂，长度增加，沿着方向的CFs突触密度降低。MSA病例和SCA 1病例的CF突触密度降低最严重，延伸到PF区域的CF明显缺乏。此外，在MSA病例的一个子集中，CF形成平行于PC层的侧支，这在其他诊断组中未见。使用无监督聚类分析，病例组和对照组均可根据CF病理和PC病理特征（包括PC计数及其轴突鱼雷）分为四类。ET病例和PD病例共分为两个聚类，而SCA 1病例和MSA病例形成另一个聚类，与对照聚类分开。有趣的是，静息震颤的存在似乎是将病例分为两个ET-PD簇的临床特征。总之，我们的研究表明，这些退行性运动障碍似乎不同的CF突触病理模式，他们表现出。这些差异如何影响这些疾病的临床表现仍有待确定。
Changes in climbing fiber-Purkinje cell (CF-PC) synaptic connections have been found in the essential tremor (ET) cerebellum, and these changes are correlated with tremor severity. Whether these postmortem changes are specific to ET remains to be investigated. We assessed CF-PC synaptic pathology in the postmortem cerebellum across a range of degenerative movement disorders [10 Parkinson's disease (PD) cases, 10 multiple system atrophy (MSA) cases, 10 spinocerebellar ataxia type 1 (SCA1) cases, and 20 ET cases] and 25 controls. We observed differences in terms of CF pathological features across these disorders. Specifically, PD cases and ET cases both had more CFs extending into the parallel fiber (PF) territory, but ET cases had more complex branching and increased length of CFs in the PF territory along with decreased CF synaptic density compared to PD cases. MSA cases and SCA1 cases had the most severely reduced CF synaptic density and a marked paucity of CFs extending into the PF territory. Furthermore, CFs in a subset of MSA cases formed collateral branches parallel to the PC layer, a feature not seen in other diagnostic groups. Using unsupervised cluster analysis, the cases and controls could all be categorized into four clusters based on the CF pathology and features of PC pathology, including counts of PCs and their axonal torpedoes. ET cases and PD cases co-segregated into two clusters, whereas SCA1 cases and MSA cases formed another cluster, separate from the control cluster. Interestingly, the presence of resting tremor seemed to be the clinical feature that separated the cases into the two ET-PD clusters. In conclusion, our study demonstrates that these degenerative movement disorders seem to differ with respect to the pattern of CF synaptic pathology they exhibit. It remains to be determined how these differences contribute to the clinical presentations of these diseases.