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Climbing fiber-Purkinje cell synaptic pathology in tremor and cerebellar degenerative diseases

Acta neuropathologica, 2017-01, Vol.133 (1), p.121-138 [Peer Reviewed Journal]

Springer-Verlag Berlin Heidelberg 2016 ;COPYRIGHT 2017 Springer ;Acta Neuropathologica is a copyright of Springer, 2017. ;ISSN: 0001-6322 ;EISSN: 1432-0533 ;DOI: 10.1007/s00401-016-1626-1 ;PMID: 27704282

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Title:
Climbing fiber-Purkinje cell synaptic pathology in tremor and cerebellar degenerative diseases
Author: Kuo, Sheng-Han ; Lin, Chi-Ying ; Wang, Jie ; Sims, Peter A. ; Pan, Ming-Kai ; Liou, Jyun-you ; Lee, Danielle ; Tate, William J. ; Kelly, Geoffrey C. ; Louis, Elan D. ; Faust, Phyllis L.
Subjects: Aged ; Aged, 80 and over ; Analysis ; Brain ; Cluster Analysis ; Essential Tremor - diagnosis ; Essential Tremor - metabolism ; Essential Tremor - pathology ; Female ; Humans ; Image Interpretation, Computer-Assisted ; Immunohistochemistry ; Male ; Medical research ; Medical schools ; Medicine ; Medicine & Public Health ; Middle Aged ; Movement disorders ; Multiple System Atrophy - diagnosis ; Multiple System Atrophy - metabolism ; Multiple System Atrophy - pathology ; Neural Pathways - metabolism ; Neural Pathways - pathology ; Neurosciences ; Olivary Nucleus - metabolism ; Olivary Nucleus - pathology ; Original Paper ; Parkinson Disease - diagnosis ; Parkinson Disease - metabolism ; Parkinson Disease - pathology ; Pathology ; Purkinje Cells - metabolism ; Purkinje Cells - pathology ; Severity of Illness Index ; Spinocerebellar Ataxias - diagnosis ; Spinocerebellar Ataxias - metabolism ; Spinocerebellar Ataxias - pathology ; Synapses - metabolism ; Synapses - pathology ; Tremor - diagnosis ; Tremor - metabolism ; Tremor - pathology ; Unsupervised Machine Learning ; Vesicular Glutamate Transport Protein 2 - metabolism
Is Part Of: Acta neuropathologica, 2017-01, Vol.133 (1), p.121-138
Description: 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.
Publisher: Berlin/Heidelberg: Springer Berlin Heidelberg
Language: English
Identifier: ISSN: 0001-6322
EISSN: 1432-0533
DOI: 10.1007/s00401-016-1626-1
PMID: 27704282
Source: ProQuest One Psychology
AUTh Library subscriptions: ProQuest Central
MEDLINE

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Climbing fiber-Purkinje cell synaptic pathology in tremor and cerebellar degenerative diseases

Springer-Verlag Berlin Heidelberg 2016 ;COPYRIGHT 2017 Springer ;Acta Neuropathologica is a copyright of Springer, 2017. ;ISSN: 0001-6322 ;EISSN: 1432-0533 ;DOI: 10.1007/s00401-016-1626-1 ;PMID: 27704282

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