Cited by 102Genetic Neurodegenerative DiseasesNeurological disorders and treatmentsNeurological diseases and metabolism

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

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Reiner, Anton, Shelby, Evan, Wang, Hongbing, DeMarch, Zena, Deng, Yunping, Guley, Natalie Hart, Hogg, Virginia, Roxburgh, Richard +3 more·2013·Movement Disorders

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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  1. Harrington KM Kowall NW Parvalbumin immunoreactive neurons resist degeneration in HD striatum J Neuropathol Exp Neurol 1991 50 309 2061713

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Authors
Reiner, A., Shelby, E., Wang, H., DeMarch, Z., Deng, Y., Guley, N. H., Hogg, V., Roxburgh, R., Tippett, L. J., Waldvogel, H. J., & Faull, R. L. M.
Affiliations
  • University of Tennessee Health Science Center (US)
  • University of Auckland (NZ)
Corresponding author
Reiner, Anton
Venue
Movement Disorders
Publisher
Wiley
Published
2013-09-03
Volume
28
Issue
12
Pages
1691-1699
ISSN
  • 0885-3185 (ISSN-L)
  • 1531-8257
OpenAlex
W1521194061
Cited by
102
References
76
Citations by year
2026: 4 · 2025: 10 · 2024: 5 · 2023: 5 · 2022: 7 · 2021: 9 · 2020: 12 · 2019: 12 · 2018: 8 · 2017: 9 · 2016: 7 · 2015: 7 · 2014: 7
FWCI
3.43
Type
journal article
Language
en
Open access
Locations
  • Movement Disorders (publishedVersion, cc-by-nc)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • University of Michigan
  • University of Rochester
  • National Institutes of Health
  • Health Science Center, University of Tennessee
  • Health Research Council of New Zealand
  • National Institute of Neurological Disorders and Stroke (NS 28721, R01NS028721, R56NS028721)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Genetic Neurodegenerative Diseases
  • Health Sciences › Medicine › Neurology › Neurological disorders and treatments
  • Life Sciences › Neuroscience › Neurology › Neurological diseases and metabolism
Keywords
Huntington's disease, dystonia, caudate nucleus, putamen, disease progression, somatostatin, neuropeptide Y, striatal atrophy
MeSH terms
Adult, Aged, Aged, 80 and over, Corpus Striatum, Dystonia, Female, Humans, Huntington Disease, Male, Middle Aged, Nerve Degeneration, Neurons, Parvalbumins

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