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Cellular localization and development of neuronal intranuclear inclusions in striatal and cortical neurons in R6/2 transgenic mice
Author(s) -
Meade Christopher A.,
Deng YunPing,
Fusco Francesca R.,
Del Mar Nobel,
Hersch Steven,
Goldowitz Dan,
Reiner Anton
Publication year - 2002
Publication title -
journal of comparative neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.855
H-Index - 209
eISSN - 1096-9861
pISSN - 0021-9967
DOI - 10.1002/cne.10295
Subject(s) - striatum , biology , parvalbumin , neuroscience , cortex (anatomy) , cerebral cortex , huntingtin , huntington's disease , calbindin , basal ganglia , medium spiny neuron , genetically modified mouse , transgene , central nervous system , pathology , dopamine , immunohistochemistry , medicine , biochemistry , disease , mutant , immunology , gene
The cellular localization and development of neuronal intranuclear inclusions (NIIs) in cortex and striatum of R6/2 HD transgenic mice were studied to ascertain the relationship of NIIs to symptom formation in these mice and gain clues regarding the possible relationship of NII formation to neuropathology in Huntington's disease (HD). All NIIs observed in R6/2 mice were ubiquitinated, and no evidence was observed for a contribution to them from wild‐type huntingtin; they were first observed in cortex and striatum at 3.5 weeks of age. In cortex, NIIs increased rapidly in size and prevalence after their appearance. Generally, cortical projection neurons developed NIIs more rapidly than cortical interneurons containing calbindin or parvalbumin. Few cortical somatostatinergic interneurons, however, formed NIIs. In striatum, calbindinergic projection neurons and parvalbuminergic interneurons rapidly formed NIIs, but they formed more gradually in cholinergic interneurons, and few somatostatinergic interneurons developed NIIs. Striatal NIIs tended to be smaller than those in cortex. The early accumulation of NIIs in cortex and striatum in R6/2 mice is consistent with the early appearance of motor and learning abnormalities in these mice, and the eventual pervasiveness of NIIs at ages at which severe abnormalities are evident is consistent with their contribution to a neuronal dysfunction underlying the abnormalities. That cortex develops larger NIIs than striatum, however, is inconsistent with the preferential loss of striatal neurons in HD but is consistent with recent evidence of early morphological abnormalities in cortical neurons in HD. That calbindinergic and parvalbuminergic striatal neurons develop large NIIs is consistent with a contribution of nuclear aggregate formation to their high degree of vulnerability in HD. J. Comp. Neurol. 449:241–269, 2002. © 2002 Wiley‐Liss, Inc.