Striatal parvalbuminergic neurons are lost in Huntington's disease

Implications for dystonia

Anton Reiner, Evan Shelby, Hongbing Wang, Zena Demarch, Yunping Deng, Natalie Hart Guley, Virginia Hogg, Richard Roxburgh, Lynette J. Tippett, Henry J. Waldvogel, Richard L.M. Faull

Research output: Contribution to journalArticle

38 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1691-1699
Number of pages9
JournalMovement Disorders
Volume28
Issue number12
DOIs
StatePublished - Oct 1 2013

Fingerprint

Corpus Striatum
Dystonia
Huntington Disease
Interneurons
Neurons
Globus Pallidus
Putamen
Neuropeptide Y
Somatostatin
Atrophy
Disease Progression

All Science Journal Classification (ASJC) codes

  • Neurology
  • Clinical Neurology

Cite this

Striatal parvalbuminergic neurons are lost in Huntington's disease : Implications for dystonia. / Reiner, Anton; Shelby, Evan; Wang, Hongbing; Demarch, Zena; Deng, Yunping; Guley, Natalie Hart; Hogg, Virginia; Roxburgh, Richard; Tippett, Lynette J.; Waldvogel, Henry J.; Faull, Richard L.M.

In: Movement Disorders, Vol. 28, No. 12, 01.10.2013, p. 1691-1699.

Research output: Contribution to journalArticle

Reiner, A, Shelby, E, Wang, H, Demarch, Z, Deng, Y, Guley, NH, Hogg, V, Roxburgh, R, Tippett, LJ, Waldvogel, HJ & Faull, RLM 2013, 'Striatal parvalbuminergic neurons are lost in Huntington's disease: Implications for dystonia', Movement Disorders, vol. 28, no. 12, pp. 1691-1699. https://doi.org/10.1002/mds.25624
Reiner, Anton ; Shelby, Evan ; Wang, Hongbing ; Demarch, Zena ; Deng, Yunping ; Guley, Natalie Hart ; Hogg, Virginia ; Roxburgh, Richard ; Tippett, Lynette J. ; Waldvogel, Henry J. ; Faull, Richard L.M. / Striatal parvalbuminergic neurons are lost in Huntington's disease : Implications for dystonia. In: Movement Disorders. 2013 ; Vol. 28, No. 12. pp. 1691-1699.
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AU - Deng, Yunping

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AU - Hogg, Virginia

AU - Roxburgh, Richard

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