Striatal parvalbuminergic neurons are lost in Huntington's disease: implications for dystonia
Open accessAbstract
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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In the anterior caudate of Huntington's disease patients, parvalbumin interneurons are reduced by roughly 75%.
“Parvalbumin interneurons are reduced in number by 75% in the anterior caudate of patients with Huntington's disease”
From Microglial depletion prevents extracellular matrix changes and striatal volume reduction in a model of Huntington's disease (2020) · cites this paper as Reiner et al., 2013
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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
- ORCID
- Venue
- Movement Disorders
- Publisher
- Wiley
- Published
- 2013-09-03
- Volume
- 28
- Issue
- 12
- Pages
- 1691-1699
- ISSN
- 0885-3185 (ISSN-L)
- 1531-8257
- PMC
- PMC3812318
- 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
- hybrid
- doi.org
- Licence
- 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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