Huntingtin localization in brains of normal and Huntington's disease patients.
The immunohistochemical localization of huntingtin was examined in the Huntington's disease (HD) brain with an antibody that recognizes the wild-type and mutant proteins. Neuronal staining was reduced in areas of the HD striatum depleted of medium-sized neurons; large striatal neurons, which are spared in HD, retained normal levels of huntingtin expression. Neuronal labeling was markedly reduced in both segments of the globus pallidus including in brains with minimal loss of pallidal neurons. In some HD cortical and striatal neurons with normal looking morphology, huntingtin was associated with punctate cytoplasmic granules that at the ultrastructural level resembled the multivesicular body, an organelle involved in retrograde transport and protein degradation. Some immunoreactive processes showed blebbing and segmentation similar to that induced experimentally by hypoxic-ischemic or excitotoxic injury. Huntingtin staining was more concentrated in the perinuclear cytoplasm and reduced or absent in processes of atrophic cortical neurons. Nuclear staining was also evident. Fibers in the subcortical white matter of HD patients had significantly increased huntingtin immunoreactivity compared with those of controls. Results suggest that there may be changes in the neuronal expression and transport of wild-type and/or mutant huntingtin at early and late stages of neuronal degeneration in affected areas of the HD brain.
Sapp
E
E
Massachusetts General Hospital, Boston, USA.
Schwarz
C
C
Chase
K
K
Bhide
P G
PG
Young
A B
AB
Penney
J
J
Vonsattel
J P
JP
Aronin
N
N
DiFiglia
M
M
D000293:Adolescent; D000368:Aged; D000906:Antibodies; D001369:Axons / Q000737:chemistry; D015153:Blotting, Western; D064026:Calbindins; D002402:Cathepsin D / Q000032:analysis; D002467:Cell Nucleus / Q000737:chemistry / Q000473:pathology; D002540:Cerebral Cortex / Q000737:chemistry* / Q000473:pathology; D003342:Corpus Striatum / Q000737:chemistry* / Q000473:pathology; D003593:Cytoplasm / Q000737:chemistry; D003712:Dendrites / Q000737:chemistry; D006801:Humans; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D007124:Immunoenzyme Techniques; D016253:Microscopy, Immunoelectron; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000032:analysis* / Q000276:immunology; D009687:Nuclear Proteins / Q000032:analysis* / Q000276:immunology; D017966:Pyramidal Cells / Q000737:chemistry / Q000648:ultrastructure; D064030:S100 Calcium Binding Protein G / Q000032:analysis; D018911:Trinucleotide Repeats / Q000235:genetics
D000906:Antibodies; D064026:Calbindins; C086055:HTT protein, human; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D064030:S100 Calcium Binding Protein G; D002402:Cathepsin D