Striatal parvalbuminergic neurons are lost in Huntington's disease: implications for dystonia
Identifieur interne : 000768 ( Main/Curation ); précédent : 000767; suivant : 000769Striatal parvalbuminergic neurons are lost in Huntington's disease: implications for dystonia
Auteurs : Anton Reiner [États-Unis] ; Evan Shelby [États-Unis] ; Hongbing Wang [États-Unis] ; Zena Demarch [États-Unis] ; Yunping Deng [États-Unis] ; Natalie Hart Guley [États-Unis] ; Virginia Hogg [Nouvelle-Zélande] ; Richard Roxburgh [Nouvelle-Zélande] ; Lynette J. Tippett [Nouvelle-Zélande] ; Henry J. Waldvogel [Nouvelle-Zélande] ; Richard Lm Faull [Nouvelle-Zélande]Source :
- Movement Disorders [ 0885-3185 ] ; 2013.
English descriptors
- KwdEn :
- Adult, Aged, Aged, 80 and over, Corpus Striatum (metabolism), Corpus Striatum (pathology), Dystonia (metabolism), Dystonia (pathology), Female, Humans, Huntington Disease (metabolism), Huntington Disease (pathology), Male, Middle Aged, Nerve Degeneration (metabolism), Nerve Degeneration (pathology), Neurons (metabolism), Neurons (pathology), Parvalbumins (metabolism).
- MESH :
- chemical , metabolism : Parvalbumins.
- metabolism : Corpus Striatum, Dystonia, Huntington Disease, Nerve Degeneration, Neurons.
- pathology : Corpus Striatum, Dystonia, Huntington Disease, Nerve Degeneration, Neurons.
- Adult, Aged, Aged, 80 and over, Female, Humans, Male, Middle Aged.
Abstract
Although dystonia represents a major source of motor disability in Huntington's disease (HD), its pathophysiology remains unknown. Because recent animal studies indicate that loss of parvalbuminergic (PARV+) striatal interneurons can cause dystonia, we investigated if loss of PARV+ striatal interneurons occurs during human HD progression, and thus might contribute to dystonia in HD. We used immunolabeling to detect PARV+ interneurons in fixed sections, and corrected for disease-related striatal atrophy by expressing PARV+ interneuron counts in ratio to interneurons co-containing somatostatin and neuropeptide Y (whose numbers are unaffected in HD). At all symptomatic HD grades, PARV+ interneurons were reduced to less than 26% of normal abundance in rostral caudate. In putamen rostral to the level of globus pallidus, loss of PARV+ interneurons was more gradual, not dropping off to less than 20% of control until grade 2. Loss of PARV+ interneurons was even more gradual in motor putamen at globus pallidus levels, with no loss at grade 1, and steady grade-wise decline thereafter. A large decrease in striatal PARV+ interneurons, thus, occurs in HD with advancing disease grade, with regional variation in the loss per grade. Given the findings of animal studies and the grade-wise loss of PARV+ striatal interneurons in motor striatum in parallel with the grade-wise appearance and worsening of dystonia, our results raise the possibility that loss of PARV+ striatal interneurons is a contributor to dystonia in HD.
Url:
DOI: 10.1002/mds.25624
PubMed: 24014043
PubMed Central: 3812318
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PMC:3812318Le document en format XML
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<author><name sortKey="Faull, Richard Lm" sort="Faull, Richard Lm" uniqKey="Faull R" first="Richard Lm" last="Faull">Richard Lm Faull</name>
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<series><title level="j">Movement Disorders</title>
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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adult</term>
<term>Aged</term>
<term>Aged, 80 and over</term>
<term>Corpus Striatum (metabolism)</term>
<term>Corpus Striatum (pathology)</term>
<term>Dystonia (metabolism)</term>
<term>Dystonia (pathology)</term>
<term>Female</term>
<term>Humans</term>
<term>Huntington Disease (metabolism)</term>
<term>Huntington Disease (pathology)</term>
<term>Male</term>
<term>Middle Aged</term>
<term>Nerve Degeneration (metabolism)</term>
<term>Nerve Degeneration (pathology)</term>
<term>Neurons (metabolism)</term>
<term>Neurons (pathology)</term>
<term>Parvalbumins (metabolism)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Parvalbumins</term>
</keywords>
<keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Corpus Striatum</term>
<term>Dystonia</term>
<term>Huntington Disease</term>
<term>Nerve Degeneration</term>
<term>Neurons</term>
</keywords>
<keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Corpus Striatum</term>
<term>Dystonia</term>
<term>Huntington Disease</term>
<term>Nerve Degeneration</term>
<term>Neurons</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Adult</term>
<term>Aged</term>
<term>Aged, 80 and over</term>
<term>Female</term>
<term>Humans</term>
<term>Male</term>
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<front><div type="abstract" xml:lang="en"><p>Although dystonia represents a major source of motor disability in Huntington's disease (HD), its pathophysiology remains unknown. Because recent animal studies indicate that loss of parvalbuminergic (PARV+) striatal interneurons can cause dystonia, we investigated if loss of PARV+ striatal interneurons occurs during human HD progression, and thus might contribute to dystonia in HD. We used immunolabeling to detect PARV+ interneurons in fixed sections, and corrected for disease-related striatal atrophy by expressing PARV+ interneuron counts in ratio to interneurons co-containing somatostatin and neuropeptide Y (whose numbers are unaffected in HD). At all symptomatic HD grades, PARV+ interneurons were reduced to less than 26% of normal abundance in rostral caudate. In putamen rostral to the level of globus pallidus, loss of PARV+ interneurons was more gradual, not dropping off to less than 20% of control until grade 2. Loss of PARV+ interneurons was even more gradual in motor putamen at globus pallidus levels, with no loss at grade 1, and steady grade-wise decline thereafter. A large decrease in striatal PARV+ interneurons, thus, occurs in HD with advancing disease grade, with regional variation in the loss per grade. Given the findings of animal studies and the grade-wise loss of PARV+ striatal interneurons in motor striatum in parallel with the grade-wise appearance and worsening of dystonia, our results raise the possibility that loss of PARV+ striatal interneurons is a contributor to dystonia in HD.</p>
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