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Mapping Purkinje Cell Placement Along the Purkinje Cell Layer: an Analysis of Postmortem Tissue from Essential Tremor Patients vs. Controls.

Authors
  • Louis, Elan D1, 2, 3
  • Rabinowitz, Daniel4
  • Choe, Matthew5
  • Tate, William J5
  • Kelly, Geoffrey C5
  • Kuo, Sheng-Han6
  • Faust, Phyllis L5
  • 1 Department of Neurology, Yale School of Medicine, Yale University, LCI 710, 15 York Street, PO Box 208018, New Haven, CT, 06520-8018, USA. [email protected]
  • 2 Department of Chronic Disease Epidemiology, Yale School of Public Health, Yale University, New Haven, CT, USA. [email protected]
  • 3 Center for Neuroepidemiology and Clinical Neurological Research, Yale School of Medicine, Yale University, New Haven, CT, USA. [email protected]
  • 4 Department of Statistics, Columbia University, New York, NY, 10032, USA.
  • 5 Department of Pathology and Cell Biology, Columbia University Medical Center and the New York Presbyterian Hospital, New York, NY, 10032, USA.
  • 6 Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY, 10032, USA.
Type
Published Article
Journal
Cerebellum (London, England)
Publication Date
December 2016
Volume
15
Issue
6
Pages
726–731
Identifiers
PMID: 26563297
Source
Medline
Keywords
License
Unknown

Abstract

Postmortem studies have reported Purkinje cell loss in essential tremor (ET), and we recently demonstrated a significant increase in the mean distance between Purkinje cell bodies (i.e., a larger gap length distance) in ET cases vs. controls, likely reflecting a disease-associated reduction in Purkinje cells. We now analyze the regularity of distribution of Purkinje cells along the Purkinje cell layer to determine whether there is greater disorganization in ET cases than in age-matched controls. A standard parasagittal, formalin-fixed, tissue block was harvested from the neocerebellum of 50 ET cases and 25 age-matched controls. The gap length distance (μm) between Purkinje cells was quantified using a nearest neighbor analysis in which the distance between each Purkinje cell body was measured in OpenLAB software, version 5 (Improvision, Waltham, MA) by drawing a freehand line between adjacent Purkinje cell bodies along the entirety of the Purkinje cell layer within a given image. We analyzed the subject-specific variation in the organization of Purkinje cells along the Purkinje cell layer. The 50 ET cases and 25 controls were similar in age at death, gender, and brain weight. Overall, greater variation in gap length distance (i.e., more disorganization) was associated with greater gap length distance (p < 0.001) and younger age (p = 0.020). However, the variation in the Purkinje cell gap length distance (i.e., Purkinje cell organization) did not differ in ET cases and controls (p = 0.330). We observed that the regularity of the distribution of Purkinje cells along the Purkinje cell layer did not differ between ET cases and controls. Several alternative biological interpretations for this finding are discussed.

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