TY - JOUR
T1 - Cellular localization of huntingtin in striatal and cortical neurons in rats
T2 - Lack of correlation with neuronal vulnerability in Huntington's disease
AU - Fusco, Francesca R.
AU - Chen, Quan
AU - Lamoreaux, William J.
AU - Figueredo-Cardenas, Griselle
AU - Jiao, Yun
AU - Coffman, Jonathan A.
AU - Surmeier, D. James
AU - Honig, Marcia G.
AU - Carlock, Leon R.
AU - Reiner, Anton
PY - 1999/2/15
Y1 - 1999/2/15
N2 - 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.
AB - 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.
KW - Cholinergic interneurons
KW - Corticostriatal neurons
KW - Huntingtin
KW - Huntington's disease
KW - Striatal projection neurons
KW - Striatum
UR - http://www.scopus.com/inward/record.url?scp=0033557661&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0033557661&partnerID=8YFLogxK
U2 - 10.1523/jneurosci.19-04-01189.1999
DO - 10.1523/jneurosci.19-04-01189.1999
M3 - Article
C2 - 9952397
AN - SCOPUS:0033557661
VL - 19
SP - 1189
EP - 1202
JO - Journal of Neuroscience
JF - Journal of Neuroscience
SN - 0270-6474
IS - 4
ER -