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).
Striatal parvalbuminergic neurons are lost in Huntington's disease: implications for dystonia
Article first published online: 3 SEP 2013
© 2013 The Authors. International Parkinson and Movement Disorder Society published by Wiley Periodicals, Inc.
This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
Volume 28, Issue 12, pages 1691–1699, October 2013
How to Cite
Reiner, A., Shelby, E., Wang, H., DeMarch, Z., Deng, Y., Guley, N. H., Hogg, V., Roxburgh, R., Tippett, L. J., Waldvogel, H. J. and Faull, R. L.M. (2013), Striatal parvalbuminergic neurons are lost in Huntington's disease: implications for dystonia. Mov. Disord., 28: 1691–1699. doi: 10.1002/mds.25624
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.
- Issue published online: 25 OCT 2013
- Article first published online: 3 SEP 2013
- Manuscript Accepted: 3 JUL 2013
- Manuscript Revised: 1 JUL 2013
- Manuscript Received: 1 MAY 2013
- Huntington's disease;
- parvalbuminergic interneurons
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.