QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (66) Citing Articles via Google Scholar Google Scholar Articles by Fusco, F. R. Articles by Reiner, A. Search for Related Content PubMed PubMed Citation Articles by Fusco, F. R. Articles by Reiner, A. Pubmed/NCBI databases Substance via MeSH Medline Plus Health Information Huntington's Disease

 Previous Article  |  Next Article 

The Journal of Neuroscience, February 15, 1999, 19(4):1189-1202

Cellular Localization of Huntingtin in Striatal and Cortical Neurons in Rats: Lack of Correlation with Neuronal Vulnerability in Huntington's Disease

Francesca R. Fusco¹, Quan Chen¹, William J. Lamoreaux², Griselle Figueredo-Cardenas¹, Yun Jiao¹, Jonathan A. Coffman¹, D. James Surmeier³, Marcia G. Honig¹, Leon R. Carlock⁴, and Anton Reiner¹

¹ Department of Anatomy and Neurobiology, College of Medicine, The University of Tennessee-Memphis, The Health Sciences Center, Memphis, Tennessee 38163, ² Department of Biology, College of Staten Island, City University of New York, Staten Island, New York 10314, ³ Department of Physiology/Northwestern University Institute for Neuroscience, Searle 5-474, Northwestern University Medical School, Chicago, Illinois 60611, and ⁴ Department of Molecular Biology and Genetics, School of Medicine, Wayne State University, Detroit, Michigan 48201

Immunohistochemistry and single-cell RT-PCR were used to characterize the localization of huntingtin and/or its mRNA in the major types of striatal neurons and in corticostriatal projection neurons in rats. Single-label immunohistochemical studies revealed that striatum contains scattered large neurons rich in huntingtin and more numerous medium-sized neurons moderate in huntingtin. Double-label immunohistochemical studies showed that the large huntingtin-rich striatal neurons include nearly all cholinergic interneurons and some parvalbuminergic interneurons. Somatostatinergic striatal interneurons, which are medium in size, rarely contained huntingtin. Calbindin immunolabeling showed that the vast majority of the medium-sized striatal neurons that contain huntingtin are projection neurons, but only ~65% of calbindin-labeled projection neurons (localized to the matrix compartment of striatum) were labeled for huntingtin. Calbindin-containing projection neurons of the matrix compartment and calbindin-negative projection neurons of the striatal patch compartment contained huntingtin with comparable frequency. Single-cell RT-PCR confirmed that striatal cholinergic interneurons contain huntingtin, but only ~65% of projection neurons contained detectable huntingtin message. The finding that huntingtin is not consistently found in striatal projection neurons [which die in Huntington's disease (HD)] but is abundant in striatal cholinergic interneurons (which survive in Huntington's disease) suggests that the mutation in huntingtin that causes HD may not directly kill neurons. In contrast to the heterogeneous expression of huntingtin in the different striatal neuron types, we found all corticostriatal neurons to be rich in huntingtin protein and mRNA. One possibility raised by our findings is that the HD mutation may render corticostriatal neurons destructive rather than render striatal neurons vulnerable.

Key words: striatum; huntingtin; corticostriatal neurons; Huntington's disease; cholinergic interneurons; striatal projection neurons

---

Copyright © 1999 Society for Neuroscience  0270-6474/99/1941189-14$05.00/0

This article has been cited by other articles:

				B. R. Miller, A. G. Walker, A. S. Shah, S. J. Barton, and G. V. Rebec Dysregulated Information Processing by Medium Spiny Neurons in Striatum of Freely Behaving Mouse Models of Huntington's Disease J Neurophysiol, October 1, 2008; 100(4): 2205 - 2216. [Abstract] [Full Text] [PDF]

				S. Cuthbertson, M. S. LeDoux, S. Jones, J. Jones, Q. Zhou, S. Gong, P. Ryan, and A. Reiner Localization of Preganglionic Neurons That Innervate Choroidal Neurons of Pterygopalatine Ganglion Invest. Ophthalmol. Vis. Sci., September 1, 2003; 44(9): 3713 - 3724. [Abstract] [Full Text] [PDF]

				C. L. Wellington, L. M. Ellerby, C.-A. Gutekunst, D. Rogers, S. Warby, R. K. Graham, O. Loubser, J. van Raamsdonk, R. Singaraja, Y.-Z. Yang, et al. Caspase Cleavage of Mutant Huntingtin Precedes Neurodegeneration in Huntington's Disease J. Neurosci., September 15, 2002; 22(18): 7862 - 7872. [Abstract] [Full Text] [PDF]

				L. B. Menalled, J. D. Sison, Y. Wu, M. Olivieri, X.-J. Li, H. Li, S. Zeitlin, and M.-F. Chesselet Early Motor Dysfunction and Striosomal Distribution of Huntingtin Microaggregates in Huntington's Disease Knock-In Mice J. Neurosci., September 15, 2002; 22(18): 8266 - 8276. [Abstract] [Full Text] [PDF]

				A. Reiner, N. Del Mar, C. A. Meade, H. Yang, I. Dragatsis, S. Zeitlin, and D. Goldowitz Neurons Lacking Huntingtin Differentially Colonize Brain and Survive in Chimeric Mice J. Neurosci., October 1, 2001; 21(19): 7608 - 7619. [Abstract] [Full Text] [PDF]

				J. F. Marshall The education of a brain transplant PNAS, August 31, 1999; 96(18): 9976 - 9978. [Full Text] [PDF]

				C. Zuccato, A. Ciammola, D. Rigamonti, B. R. Leavitt, D. Goffredo, L. Conti, M. E. MacDonald, R. M. Friedlander, V. Silani, M. R. Hayden, et al. Loss of Huntingtin-Mediated BDNF Gene Transcription in Huntington's Disease Science, July 20, 2001; 293(5529): 493 - 498. [Abstract] [Full Text] [PDF]

				Y. F. Liu, D. Dorow, and J. Marshall Activation of MLK2-mediated Signaling Cascades by Polyglutamine-expanded Huntingtin J. Biol. Chem., June 16, 2000; 275(25): 19035 - 19040. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help