Striatal parvalbuminergic neurons are lost in Huntington's disease: implications for dystonia

Authors

  • Anton Reiner PhD,

    Corresponding author
    1. Department of Anatomy and Neurobiology, The University of Tennessee Health Science Center, Memphis, Tennessee, USA
    • Correspondence to: Dr. Anton Reiner, Department of Anatomy and Neurobiology, The University of Tennessee Health Science Center, 855 Monroe Ave., Memphis, TN 38163, USA; areiner@uthsc.edu

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  • Evan Shelby MD,

    1. Department of Anatomy and Neurobiology, The University of Tennessee Health Science Center, Memphis, Tennessee, USA
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  • Hongbing Wang PhD,

    1. Department of Anatomy and Neurobiology, The University of Tennessee Health Science Center, Memphis, Tennessee, USA
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  • Zena DeMarch PhD,

    1. Department of Anatomy and Neurobiology, The University of Tennessee Health Science Center, Memphis, Tennessee, USA
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  • Yunping Deng MD,

    1. Department of Anatomy and Neurobiology, The University of Tennessee Health Science Center, Memphis, Tennessee, USA
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  • Natalie Hart Guley BA,

    1. Department of Anatomy and Neurobiology, The University of Tennessee Health Science Center, Memphis, Tennessee, USA
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  • Virginia Hogg MA,

    1. Centre for Brain Research, University of Auckland, Auckland, New Zealand
    2. Department of Psychology, University of Auckland, Auckland, New Zealand
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  • Richard Roxburgh PhD,

    1. Centre for Brain Research, University of Auckland, Auckland, New Zealand
    2. Department of Neurology, Auckland City Hospital, Auckland, New Zealand
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  • Lynette J. Tippett PhD,

    1. Centre for Brain Research, University of Auckland, Auckland, New Zealand
    2. Department of Psychology, University of Auckland, Auckland, New Zealand
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  • Henry J. Waldvogel PhD,

    1. Centre for Brain Research, University of Auckland, Auckland, New Zealand
    2. Department of Anatomy with Radiology, University of Auckland, Auckland, New Zealand
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  • Richard L.M. Faull DSc

    1. Centre for Brain Research, University of Auckland, Auckland, New Zealand
    2. Department of Anatomy with Radiology, University of Auckland, Auckland, New Zealand
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  • Funding agencies: Santa Lucia Foundation IRCSS at the European Center for Brain Research (ZM), NIH NS-28721 (AR), Hereditary Disease Foundation (AR), The Methodist Hospitals Endowed Professorship in Neuroscience (AR), the Matthew Oswin Memorial Trust (RLMF), and the Health Research Council of New Zealand (RLMF).

  • Relevant conflicts of interest/financial disclosures: Nothing to report.

  • Full financial disclosures and author roles may be found in the online version of this article.

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.

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