Movement Disorders (revue)

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Quantification of Cerebellar Hemispheric Purkinje Cell Linear Density: 32 ET Cases vs. 16 Controls

Identifieur interne : 003D01 ( Ncbi/Merge ); précédent : 003D00; suivant : 003D02

Quantification of Cerebellar Hemispheric Purkinje Cell Linear Density: 32 ET Cases vs. 16 Controls

Auteurs : Elan D. Louis [États-Unis] ; Rachel Babij [États-Unis] ; Michelle Lee [États-Unis] ; Etty Cortés [États-Unis] ; Jean-Paul G. Vonsattel [États-Unis]

Source :

RBID : PMC:3830681

English descriptors

Abstract

Background

Although essential tremor (ET) is among the most prevalent neurological diseases, its precise pathogenesis is not understood. Purkinje cell loss has been observed in some studies and is the focus of interest and debate. Expressing these data as Purkinje cells/layer length allows one to adjust for the inherent curved nature of the cerebellar folia. Capitalizing on the Essential Tremor Centralized Brain Repository, we quantified Purkinje cell linear density in cases vs. controls.

Methods

Free-floating, 100 μm, parasagittal cerebellar hemispheric sections were subjected to rabbit polyclonal anti-Calbindin D28k antibody, and 10 random fields/brain were selected for quantification of Purkinje cells/mm−1 Purkinje cell layer.

Results

Purkinje cell linear density was lower in 32 ET cases than 16 controls (1.14 ± 0.32 vs. 1.35 ± 0.31 per mm−1, p = 0.03). Purkinje cell linear density was inversely associated with torpedo count (r = −0.38, p = 0.028).

Discussion

The current sample of ET cases demonstrates a reduction in Purkinje cell number relative to that of controls. Greater Purkinje cell axonal remodeling (torpedoes) was found in individuals who had the most Purkinje cell drop out. The role of Purkinje cell loss in the pathogenesis of this disorder merits additional study.


Url:
DOI: 10.1002/mds.25629
PubMed: 23925732
PubMed Central: 3830681

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PMC:3830681

Le document en format XML

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<name sortKey="Babij, Rachel" sort="Babij, Rachel" uniqKey="Babij R" first="Rachel" last="Babij">Rachel Babij</name>
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<title level="j">Movement disorders : official journal of the Movement Disorder Society</title>
<idno type="ISSN">0885-3185</idno>
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<term>Aged</term>
<term>Aged, 80 and over</term>
<term>Calbindin 1 (metabolism)</term>
<term>Cell Count</term>
<term>Cerebellum (pathology)</term>
<term>Essential Tremor (pathology)</term>
<term>Female</term>
<term>Functional Laterality</term>
<term>Humans</term>
<term>Male</term>
<term>Purkinje Cells (metabolism)</term>
<term>Purkinje Cells (pathology)</term>
<term>Statistics, Nonparametric</term>
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<term>Calbindin 1</term>
</keywords>
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<term>Purkinje Cells</term>
</keywords>
<keywords scheme="MESH" qualifier="pathology" xml:lang="en">
<term>Cerebellum</term>
<term>Essential Tremor</term>
<term>Purkinje Cells</term>
</keywords>
<keywords scheme="MESH" xml:lang="en">
<term>Aged</term>
<term>Aged, 80 and over</term>
<term>Cell Count</term>
<term>Female</term>
<term>Functional Laterality</term>
<term>Humans</term>
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<div type="abstract" xml:lang="en">
<sec id="S1">
<title>Background</title>
<p id="P1">Although essential tremor (ET) is among the most prevalent neurological diseases, its precise pathogenesis is not understood. Purkinje cell loss has been observed in some studies and is the focus of interest and debate. Expressing these data as Purkinje cells/layer length allows one to adjust for the inherent curved nature of the cerebellar folia. Capitalizing on the Essential Tremor Centralized Brain Repository, we quantified Purkinje cell linear density in cases vs. controls.</p>
</sec>
<sec id="S2">
<title>Methods</title>
<p id="P2">Free-floating, 100 μm, parasagittal cerebellar hemispheric sections were subjected to rabbit polyclonal anti-Calbindin D28k antibody, and 10 random fields/brain were selected for quantification of Purkinje cells/mm
<sup>−1</sup>
Purkinje cell layer.</p>
</sec>
<sec id="S3">
<title>Results</title>
<p id="P3">Purkinje cell linear density was lower in 32 ET cases than 16 controls (1.14 ± 0.32 vs. 1.35 ± 0.31 per mm
<sup>−1</sup>
, p = 0.03). Purkinje cell linear density was inversely associated with torpedo count (r = −0.38, p = 0.028).</p>
</sec>
<sec id="S4">
<title>Discussion</title>
<p id="P4">The current sample of ET cases demonstrates a reduction in Purkinje cell number relative to that of controls. Greater Purkinje cell axonal remodeling (torpedoes) was found in individuals who had the most Purkinje cell drop out. The role of Purkinje cell loss in the pathogenesis of this disorder merits additional study.</p>
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<title xml:lang="en" level="a" type="main">Quantification of Cerebellar Hemispheric Purkinje Cell Linear Density: 32 ET Cases vs. 16 Controls</title>
<author>
<name sortKey="Louis, Elan D" sort="Louis, Elan D" uniqKey="Louis E" first="Elan D." last="Louis">Elan D. Louis</name>
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<nlm:aff id="A1"> GH Sergievsky Center, College of Physicians and Surgeons, Columbia University, New York, NY, USA.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">États-Unis</country>
<wicri:regionArea> GH Sergievsky Center, College of Physicians and Surgeons, Columbia University, New York, NY</wicri:regionArea>
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<region type="state">État de New York</region>
<settlement type="city">New York</settlement>
</placeName>
<orgName type="university">Université Columbia</orgName>
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<affiliation wicri:level="4">
<nlm:aff id="A2"> Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, NY, USA.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">États-Unis</country>
<wicri:regionArea> Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, NY</wicri:regionArea>
<placeName>
<region type="state">État de New York</region>
<settlement type="city">New York</settlement>
</placeName>
<orgName type="university">Université Columbia</orgName>
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<affiliation wicri:level="4">
<nlm:aff id="A3"> Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY, USA.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">États-Unis</country>
<wicri:regionArea> Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY</wicri:regionArea>
<placeName>
<region type="state">État de New York</region>
<settlement type="city">New York</settlement>
</placeName>
<orgName type="university">Université Columbia</orgName>
</affiliation>
<affiliation wicri:level="4">
<nlm:aff id="A4"> Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">États-Unis</country>
<wicri:regionArea> Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY</wicri:regionArea>
<placeName>
<region type="state">État de New York</region>
<settlement type="city">New York</settlement>
</placeName>
<orgName type="university">Université Columbia</orgName>
</affiliation>
</author>
<author>
<name sortKey="Babij, Rachel" sort="Babij, Rachel" uniqKey="Babij R" first="Rachel" last="Babij">Rachel Babij</name>
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<nlm:aff id="A1"> GH Sergievsky Center, College of Physicians and Surgeons, Columbia University, New York, NY, USA.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">États-Unis</country>
<wicri:regionArea> GH Sergievsky Center, College of Physicians and Surgeons, Columbia University, New York, NY</wicri:regionArea>
<placeName>
<region type="state">État de New York</region>
<settlement type="city">New York</settlement>
</placeName>
<orgName type="university">Université Columbia</orgName>
</affiliation>
</author>
<author>
<name sortKey="Lee, Michelle" sort="Lee, Michelle" uniqKey="Lee M" first="Michelle" last="Lee">Michelle Lee</name>
<affiliation wicri:level="4">
<nlm:aff id="A1"> GH Sergievsky Center, College of Physicians and Surgeons, Columbia University, New York, NY, USA.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">États-Unis</country>
<wicri:regionArea> GH Sergievsky Center, College of Physicians and Surgeons, Columbia University, New York, NY</wicri:regionArea>
<placeName>
<region type="state">État de New York</region>
<settlement type="city">New York</settlement>
</placeName>
<orgName type="university">Université Columbia</orgName>
</affiliation>
</author>
<author>
<name sortKey="Cortes, Etty" sort="Cortes, Etty" uniqKey="Cortes E" first="Etty" last="Cortés">Etty Cortés</name>
<affiliation wicri:level="2">
<nlm:aff id="A5"> Department of Pathology and Cell Biology, Columbia University Medical Center and the New York Presbyterian Hospital, New York, NY, USA.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">États-Unis</country>
<wicri:regionArea> Department of Pathology and Cell Biology, Columbia University Medical Center and the New York Presbyterian Hospital, New York, NY</wicri:regionArea>
<placeName>
<region type="state">État de New York</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Vonsattel, Jean Paul G" sort="Vonsattel, Jean Paul G" uniqKey="Vonsattel J" first="Jean-Paul G." last="Vonsattel">Jean-Paul G. Vonsattel</name>
<affiliation wicri:level="4">
<nlm:aff id="A2"> Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, NY, USA.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">États-Unis</country>
<wicri:regionArea> Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, NY</wicri:regionArea>
<placeName>
<region type="state">État de New York</region>
<settlement type="city">New York</settlement>
</placeName>
<orgName type="university">Université Columbia</orgName>
</affiliation>
<affiliation wicri:level="2">
<nlm:aff id="A5"> Department of Pathology and Cell Biology, Columbia University Medical Center and the New York Presbyterian Hospital, New York, NY, USA.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">États-Unis</country>
<wicri:regionArea> Department of Pathology and Cell Biology, Columbia University Medical Center and the New York Presbyterian Hospital, New York, NY</wicri:regionArea>
<placeName>
<region type="state">État de New York</region>
</placeName>
</affiliation>
</author>
</analytic>
<series>
<title level="j">Movement disorders : official journal of the Movement Disorder Society</title>
<idno type="ISSN">0885-3185</idno>
<idno type="eISSN">1531-8257</idno>
<imprint>
<date when="2013">2013</date>
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<div type="abstract" xml:lang="en">
<sec id="S1">
<title>Background</title>
<p id="P1">Although essential tremor (ET) is among the most prevalent neurological diseases, its precise pathogenesis is not understood. Purkinje cell loss has been observed in some studies and is the focus of interest and debate. Expressing these data as Purkinje cells/layer length allows one to adjust for the inherent curved nature of the cerebellar folia. Capitalizing on the Essential Tremor Centralized Brain Repository, we quantified Purkinje cell linear density in cases vs. controls.</p>
</sec>
<sec id="S2">
<title>Methods</title>
<p id="P2">Free-floating, 100 μm, parasagittal cerebellar hemispheric sections were subjected to rabbit polyclonal anti-Calbindin D28k antibody, and 10 random fields/brain were selected for quantification of Purkinje cells/mm
<sup>−1</sup>
Purkinje cell layer.</p>
</sec>
<sec id="S3">
<title>Results</title>
<p id="P3">Purkinje cell linear density was lower in 32 ET cases than 16 controls (1.14 ± 0.32 vs. 1.35 ± 0.31 per mm
<sup>−1</sup>
, p = 0.03). Purkinje cell linear density was inversely associated with torpedo count (r = −0.38, p = 0.028).</p>
</sec>
<sec id="S4">
<title>Discussion</title>
<p id="P4">The current sample of ET cases demonstrates a reduction in Purkinje cell number relative to that of controls. Greater Purkinje cell axonal remodeling (torpedoes) was found in individuals who had the most Purkinje cell drop out. The role of Purkinje cell loss in the pathogenesis of this disorder merits additional study.</p>
</sec>
</div>
</front>
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<affiliation wicri:level="4">
<nlm:affiliation>GH Sergievsky Center, College of Physicians and Surgeons, Columbia University, New York, NY, USA; Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, New York, USA; Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, New York, USA; Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York, USA.</nlm:affiliation>
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<region type="state">État de New York</region>
<settlement type="city">New York</settlement>
</placeName>
<orgName type="university">Université Columbia</orgName>
</affiliation>
</author>
<author>
<name sortKey="Babij, Rachel" sort="Babij, Rachel" uniqKey="Babij R" first="Rachel" last="Babij">Rachel Babij</name>
</author>
<author>
<name sortKey="Lee, Michelle" sort="Lee, Michelle" uniqKey="Lee M" first="Michelle" last="Lee">Michelle Lee</name>
</author>
<author>
<name sortKey="Cortes, Etty" sort="Cortes, Etty" uniqKey="Cortes E" first="Etty" last="Cortés">Etty Cortés</name>
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<author>
<name sortKey="Vonsattel, Jean Paul G" sort="Vonsattel, Jean Paul G" uniqKey="Vonsattel J" first="Jean-Paul G" last="Vonsattel">Jean-Paul G. Vonsattel</name>
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<idno type="RBID">pubmed:23925732</idno>
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<idno type="doi">10.1002/mds.25629</idno>
<idno type="wicri:Area/PubMed/Corpus">000795</idno>
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<idno type="wicri:Area/PubMed/Checkpoint">000835</idno>
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<nlm:affiliation>GH Sergievsky Center, College of Physicians and Surgeons, Columbia University, New York, NY, USA; Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, New York, USA; Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, New York, USA; Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York, USA.</nlm:affiliation>
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<region type="state">État de New York</region>
<settlement type="city">New York</settlement>
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<name sortKey="Babij, Rachel" sort="Babij, Rachel" uniqKey="Babij R" first="Rachel" last="Babij">Rachel Babij</name>
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<name sortKey="Lee, Michelle" sort="Lee, Michelle" uniqKey="Lee M" first="Michelle" last="Lee">Michelle Lee</name>
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<name sortKey="Vonsattel, Jean Paul G" sort="Vonsattel, Jean Paul G" uniqKey="Vonsattel J" first="Jean-Paul G" last="Vonsattel">Jean-Paul G. Vonsattel</name>
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<title level="j">Movement disorders : official journal of the Movement Disorder Society</title>
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<term>Aged</term>
<term>Aged, 80 and over</term>
<term>Calbindin 1 (metabolism)</term>
<term>Cell Count</term>
<term>Cerebellum (pathology)</term>
<term>Essential Tremor (pathology)</term>
<term>Female</term>
<term>Functional Laterality</term>
<term>Humans</term>
<term>Male</term>
<term>Purkinje Cells (metabolism)</term>
<term>Purkinje Cells (pathology)</term>
<term>Statistics, Nonparametric</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en">
<term>Calbindin 1</term>
</keywords>
<keywords scheme="MESH" qualifier="metabolism" xml:lang="en">
<term>Purkinje Cells</term>
</keywords>
<keywords scheme="MESH" qualifier="pathology" xml:lang="en">
<term>Cerebellum</term>
<term>Essential Tremor</term>
<term>Purkinje Cells</term>
</keywords>
<keywords scheme="MESH" xml:lang="en">
<term>Aged</term>
<term>Aged, 80 and over</term>
<term>Cell Count</term>
<term>Female</term>
<term>Functional Laterality</term>
<term>Humans</term>
<term>Male</term>
<term>Statistics, Nonparametric</term>
</keywords>
</textClass>
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<front>
<div type="abstract" xml:lang="en">Although essential tremor (ET) is among the most prevalent neurological diseases, its precise pathogenesis is not understood. Purkinje cell loss has been observed in some studies and is the focus of interest and debate. Expressing these data as Purkinje cells/layer length allows one to adjust for the inherent curved nature of the cerebellar folia. Capitalizing on the Essential Tremor Centralized Brain Repository, we quantified Purkinje cell linear density in cases versus controls. Free-floating 100-μm parasagittal cerebellar hemispheric sections were subjected to rabbit polyclonal anti-Calbindin D28k antibody, and 10 random fields/brain were selected for quantification of Purkinje cells/mm(-1) Purkinje cell layer. Purkinje cell linear density was lower in 32 ET cases than in16 controls (1.14 ± 0.32 vs. 1.35 ± 0.31/mm(-1) , P = 0.03). Purkinje cell linear density was inversely associated with torpedo count (r = -0.38, P = 0.028). The current sample of ET cases demonstrates a reduction in Purkinje cell number relative to that of controls. Greater Purkinje cell axonal remodeling (torpedoes) was found in individuals who had the most Purkinje cell drop out. The role of Purkinje cell loss in the pathogenesis of this disorder merits additional study.</div>
</front>
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