Reduced Bergmann glial process terminations and lateral appendages in essential tremor

Abstract Objective Postmortem examination of the essential tremor cerebellum has revealed a variety of pathological changes centered in and around Purkinje cells. Studies have predominantly focused on cerebellar neuronal connections. Bergmann glial morphology has not yet been studied in essential tr...

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Main Authors: David S. Ruff, Ilaria Balbo, Ruo‐Yah Lai, Diarra Dieng, Charlotte Hennessey, Krish Vennam, Andrew J. Dwork, Morgan McCreary, Elan D. Louis, Phyllis L. Faust, Sheng‐Han Kuo
Format: Article
Language:English
Published: Wiley 2024-02-01
Series:Annals of Clinical and Translational Neurology
Online Access:https://doi.org/10.1002/acn3.51958
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author David S. Ruff
Ilaria Balbo
Ruo‐Yah Lai
Diarra Dieng
Charlotte Hennessey
Krish Vennam
Andrew J. Dwork
Morgan McCreary
Elan D. Louis
Phyllis L. Faust
Sheng‐Han Kuo
author_facet David S. Ruff
Ilaria Balbo
Ruo‐Yah Lai
Diarra Dieng
Charlotte Hennessey
Krish Vennam
Andrew J. Dwork
Morgan McCreary
Elan D. Louis
Phyllis L. Faust
Sheng‐Han Kuo
author_sort David S. Ruff
collection DOAJ
description Abstract Objective Postmortem examination of the essential tremor cerebellum has revealed a variety of pathological changes centered in and around Purkinje cells. Studies have predominantly focused on cerebellar neuronal connections. Bergmann glial morphology has not yet been studied in essential tremor. Among their many roles, Bergmann glia in the cerebellar cortex ensheath Purkinje cell synapses and provide neuroprotection. Specifically, the complex radial processes and lateral appendages of Bergmann glia are structural domains that modulate Purkinje cell synaptic transmission. In this study, we investigate whether Bergmann glia morphology is altered in the essential tremor cerebellum. Methods We applied the Golgi‐Kopsch method and used computerized three‐dimensional cell reconstruction to visualize Bergmann glia in the postmortem cerebellum of 34 cases and 17 controls. We quantified morphology of terminal structures (number of terminations and lateral appendage density) and morphology of radial processes (total process length, branch length, branch order, and branch volume) in each glial cell. We quantified number of branches and volume as well. Results Essential tremor cases had a 31.9% decrease in process terminations and a 35.7% decrease in lateral appendage density in Bergmann glia. Total process length and branch length did not differ between essential tremor cases and controls. We found also a reduction in number of secondary and tertiary branches and tertiary branches volume. Interpretation These findings suggest that Bergmann glia in essential tremor cases have more alterations in their terminal structures, with a relative preservation of radial processes, and highlight a potential role for these astrocytes in the disease pathophysiology.
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spelling doaj.art-4b5a027e77934becaa5a906e6df8f2362024-02-13T18:30:43ZengWileyAnnals of Clinical and Translational Neurology2328-95032024-02-0111237738810.1002/acn3.51958Reduced Bergmann glial process terminations and lateral appendages in essential tremorDavid S. Ruff0Ilaria Balbo1Ruo‐Yah Lai2Diarra Dieng3Charlotte Hennessey4Krish Vennam5Andrew J. Dwork6Morgan McCreary7Elan D. Louis8Phyllis L. Faust9Sheng‐Han Kuo10Department of Neurology Columbia University New York New York 10032 USADepartment of Neurology Columbia University New York New York 10032 USADepartment of Neurology Columbia University New York New York 10032 USADepartment of Neurology Columbia University New York New York 10032 USADepartment of Neurology Columbia University New York New York 10032 USADepartment of Neurology Columbia University New York New York 10032 USADepartment of Pathology and Cell Biology Columbia University Medical Center, The New York Presbyterian Hospital New York New York 10032 USADepartment of Neurology University of Texas Southwestern Dallas Texas 75390 USADepartment of Neurology University of Texas Southwestern Dallas Texas 75390 USAInitiative for Columbia Ataxia and Tremor Columbia University New York New York 10032 USADepartment of Neurology Columbia University New York New York 10032 USAAbstract Objective Postmortem examination of the essential tremor cerebellum has revealed a variety of pathological changes centered in and around Purkinje cells. Studies have predominantly focused on cerebellar neuronal connections. Bergmann glial morphology has not yet been studied in essential tremor. Among their many roles, Bergmann glia in the cerebellar cortex ensheath Purkinje cell synapses and provide neuroprotection. Specifically, the complex radial processes and lateral appendages of Bergmann glia are structural domains that modulate Purkinje cell synaptic transmission. In this study, we investigate whether Bergmann glia morphology is altered in the essential tremor cerebellum. Methods We applied the Golgi‐Kopsch method and used computerized three‐dimensional cell reconstruction to visualize Bergmann glia in the postmortem cerebellum of 34 cases and 17 controls. We quantified morphology of terminal structures (number of terminations and lateral appendage density) and morphology of radial processes (total process length, branch length, branch order, and branch volume) in each glial cell. We quantified number of branches and volume as well. Results Essential tremor cases had a 31.9% decrease in process terminations and a 35.7% decrease in lateral appendage density in Bergmann glia. Total process length and branch length did not differ between essential tremor cases and controls. We found also a reduction in number of secondary and tertiary branches and tertiary branches volume. Interpretation These findings suggest that Bergmann glia in essential tremor cases have more alterations in their terminal structures, with a relative preservation of radial processes, and highlight a potential role for these astrocytes in the disease pathophysiology.https://doi.org/10.1002/acn3.51958
spellingShingle David S. Ruff
Ilaria Balbo
Ruo‐Yah Lai
Diarra Dieng
Charlotte Hennessey
Krish Vennam
Andrew J. Dwork
Morgan McCreary
Elan D. Louis
Phyllis L. Faust
Sheng‐Han Kuo
Reduced Bergmann glial process terminations and lateral appendages in essential tremor
Annals of Clinical and Translational Neurology
title Reduced Bergmann glial process terminations and lateral appendages in essential tremor
title_full Reduced Bergmann glial process terminations and lateral appendages in essential tremor
title_fullStr Reduced Bergmann glial process terminations and lateral appendages in essential tremor
title_full_unstemmed Reduced Bergmann glial process terminations and lateral appendages in essential tremor
title_short Reduced Bergmann glial process terminations and lateral appendages in essential tremor
title_sort reduced bergmann glial process terminations and lateral appendages in essential tremor
url https://doi.org/10.1002/acn3.51958
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