title: Cell type-specific localization of optineurin in the striatal neurons of mice: implications for neuronal vulnerability in Huntington's disease.
abstract: Striatal neuropathology of Huntington's disease (HD) involves primary and progressive degeneration of the medium-sized projection neurons, with relative sparing of the local circuit interneurons. The mechanism for such a patterned cell loss in the HD striatum continues to remain unclear. Optineurin (OPTN) is one of the proteins interacting with huntingtin and plays a protective role in several neurodegenerative disorders. To determine the cellular localization pattern of OPTN in the mouse striatum, we employed a highly sensitive immunohistochemistry with the tyramide signal amplification system. In this study, we show that OPTN appeared as a cytoplasmic protein within the subsets of the striatal neurons. Of particular interest was that OPTN was abundantly expressed in the interneurons, whereas low levels of OPTN were observed in the medium projection neurons. This cell type-specific distribution of OPTN in the striatum is strikingly complementary to the pattern of neuronal loss typically observed in the striatum of patients with HD. We suggest that OPTN abundance is an important cellular factor in considering the cell type-specific vulnerability of striatal neurons in HD.
authors.affiliation: Parkinson's Disease and Dystonia Research Center, Tokushima University Hospital, University of Tokushima, Tokushima 770-8503, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Okita
authors.forename: R
authors.initials: R
authors.lastname: Morigaki
authors.forename: H
authors.initials: H
authors.lastname: Koizumi
authors.forename: R
authors.initials: R
authors.lastname: Kaji
authors.forename: S
authors.initials: S
authors.lastname: Nagahiro
authors.forename: S
authors.initials: S
authors.lastname: Goto
mesh_terms: D000818:Animals; D015153:Blotting, Western; D018797:Cell Cycle Proteins; D016923:Cell Death / Q000502:physiology; D003342:Corpus Striatum / Q000378:metabolism* / Q000473:pathology*; D003720:Densitometry; D005136:Eye Proteins / Q000378:metabolism*; D018698:Glutamic Acid / Q000633:toxicity; D006816:Huntington Disease / Q000378:metabolism* / Q000473:pathology*; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D007395:Interneurons / Q000378:metabolism / Q000473:pathology; D008297:Male; D026901:Membrane Transport Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics / Q000502:physiology; D009474:Neurons / Q000378:metabolism* / Q000473:pathology*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; D005136:Eye Proteins; D026901:Membrane Transport Proteins; C501288:Optn protein, mouse; D050486:Serotonin Plasma Membrane Transport Proteins; C493231:Slc6a4 protein, mouse; D018698:Glutamic Acid