Cellular localization of huntingtin in striatal and cortical neurons in rats: Lack of correlation with neuronal vulnerability in Huntington's disease

Francesca R. Fusco, Quan Chen, William J. Lamoreaux, Griselle Figueredo-Cardenas, Yun Jiao, Jonathan A. Coffman, D. James Surmeier, Marcia G. Honig, Leon R. Carlock, Anton Reiner

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)1189-1202
Number of pages14
JournalJournal of Neuroscience
Volume19
Issue number4
Publication statusPublished - Feb 15 1999

    Fingerprint

Keywords

  • Cholinergic interneurons
  • Corticostriatal neurons
  • Huntingtin
  • Huntington's disease
  • Striatal projection neurons
  • Striatum

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Fusco, F. R., Chen, Q., Lamoreaux, W. J., Figueredo-Cardenas, G., Jiao, Y., Coffman, J. A., Surmeier, D. J., Honig, M. G., Carlock, L. R., & Reiner, A. (1999). Cellular localization of huntingtin in striatal and cortical neurons in rats: Lack of correlation with neuronal vulnerability in Huntington's disease. Journal of Neuroscience, 19(4), 1189-1202.