Heterogeneous topographic and cellular distribution of Huntington expression in the normal human neostriatum

• Type of Material: Article
• Authors: Robert J Ferrante, Boston University School of Medicine; Claire-Anne Gutekunst, Emory University; Francesca Persichetti, Massachusetts General Hospital; Sandra M McNeil, Massachusetts General Hospital; Neil W Kowall, Boston University School of Medicine; James F Gusella, Massachusetts General Hospital; Marcy E MacDonald, Massachusetts General Hospital; M Flint Beal, Harvard Medical School; Steven M Hersch, Emory University
• Language: English
• Date: 1997-05-01
• Publisher: Society for Neuroscience
• Publication Version: Final Published Version
• Copyright Statement: © 1997 Society for Neuroscience
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1523/jneurosci.17-09-03052.1997
• Title of Journal or Parent Work: Journal of Neuroscience
• Volume: 17
• Issue: 9
• Start Page: 3052
• End Page: 3063
• Grant/Funding Information: This work was supported by the Huntington’s Disease Society of America (R.J.F.), the Department of Veterans Affairs (R.J.F., N.W.K.), the Emory University Research Committee (S.M.H.), the Huntington’s Disease Foundation (C.A.G.), and National Institutes of Health Grants AG12922 (R.J.F., M.F.B., N.W.K.), 1P30AG13846 (R.J.F., N.W.K.), NS16367 and NS10828 (M.F.B.), NS16367 (J.F.G., F.P., S.M.M., M.E.M.), NS01624 (S.M.H.), and NS35255 (S.M.H., C.A.G., R.J.F.).
• Keywords: Neurosciences; SPINY NEURONS; WIDESPREAD EXPRESSION; DISEASE GENE HOMOLOG; CALCIUM-BINDING PROTEIN; Huntington's disease; BRAIN; Science & Technology; BASAL GANGLIA; SUBSTANCE-P; NADPH-DIAPHORASE; Huntington; RAT; immunofluorescence; Neurosciences & Neurology; calbindin D28k; STRIATAL NEURONS; NADPH-diaphorase; nitric oxide synthase; Life Sciences & Biomedicine; neostriatum
• Research Categories: Biology, Neuroscience; Health Sciences, Medicine and Surgery; Biology, Molecular

Abstract

A striking heterogeneous distribution of topographic and cellular huntingtin immunoreactivity was observed within the human neostriatum using three distinct huntingtin antibodies. Patchy areas of low huntingtin immunoreactivity were present in both the caudate nucleus and putamen, surrounded by an intervening area of greater immunoreactivity. Comparison of huntingtin immunoreactivity with contiguous serial sections stained for enkephalin and calbindin D28k immunoreactivities showed that the topographic heterogeneity of huntingtin immunostaining corresponded to the patch (striosome) and matrix compartments within the striatum. Huntingtin immunoreactivity was confined primarily to neurons and neuropil within the matrix compartment, whereas little or no neuronal or neuropil huntingtin immunostaining was observed within the patch compartment. There was marked variability in the intensity of huntingtin immunolabel among medium-sized striatal neurons, whereas a majority of large striatal neurons were only faintly positive or without any immunoreactivity. Combined techniques for NADPH-diaphorase enzyme histochemistry and huntingtin immunocytochemistry, as well as double immunofluorescence for either nitric oxide synthase or calbindin D28k in comparison with huntingtin expression, revealed a striking correspondence between calbindin D28k and huntingtin immunoreactivities, with little or no colocalization between NADPH-diaphorase or nitric oxide synthase neurons and huntingtin expression. These observations suggest that the selective vulnerability of spiny striatal neurons and the matrix compartment observed in Huntington's disease is associated with higher levels of huntingtin expression, whereas the relative resistance of large and medium- sized aspiny neurons and the patch compartments to degeneration is associated with low levels of huntingtin expression.