title: Defects in the striatal neuropeptide Y system in X-linked dystonia-parkinsonism.
abstract: Neuropeptide Y is a novel bioactive substance that plays a role in the modulation of neurogenesis and neurotransmitter release, and thereby exerts a protective influence against neurodegeneration. Using a sensitive immunohistochemical method with a tyramide signal amplification protocol, we performed a post-mortem analysis to determine the striatal localization profile of neuropeptide Y in neurologically normal individuals and in patients with X-linked dystonia-parkinsonism, a major representative of the neurodegenerative diseases that primarily involve the striatum. All of the patients examined were genetically verified as having X-linked dystonia-parkinsonism. In normal individuals, we found a scattered distribution of neuropeptide Y-positive neurons and numerous nerve fibres labelled for neuropeptide Y in the striatum. Of particular interest was a differential localization of neuropeptide Y immunoreactivity in the striatal compartments, with a heightened density of neuropeptide Y labelling in the matrix compartment relative to the striosomes. In patients with X-linked dystonia-parkinsonism, we found a significant decrease in the number of neuropeptide Y-positive cells accompanied by a marked loss of their nerve fibres in the caudate nucleus and putamen. The patients with X-linked dystonia-parkinsonism also showed a lack of neuropeptide Y labelling in the subventricular zone, where a marked loss of progenitor cells that express proliferating cell nuclear antigen was found. Our results indicate a neostriatal defect of the neuropeptide Y system in patients with X-linked dystonia-parkinsonism, suggesting its possible implication in the mechanism by which a progressive loss of striatal neurons occurs in X-linked dystonia-parkinsonism.
authors.affiliation: Parkinson’s Disease and Dystonia Research Centre, Tokushima University Hospital, University of Tokushima, Tokushima 770-8503, Japan. sgoto@clin.med.tokushima-u.ac.jp
authors.forename: Satoshi
authors.initials: S
authors.lastname: Goto
authors.forename: Toshitaka
authors.initials: T
authors.lastname: Kawarai
authors.forename: Ryoma
authors.initials: R
authors.lastname: Morigaki
authors.forename: Shinya
authors.initials: S
authors.lastname: Okita
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Koizumi
authors.forename: Shinji
authors.initials: S
authors.lastname: Nagahiro
authors.forename: Edwin L
authors.initials: EL
authors.lastname: Munoz
authors.forename: Lillian V
authors.initials: LV
authors.lastname: Lee
authors.forename: Ryuji
authors.initials: R
authors.lastname: Kaji
mesh_terms: D000328:Adult; D000368:Aged; D003342:Corpus Striatum / Q000378:metabolism* / Q000473:pathology*; D020821:Dystonic Disorders / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D040181:Genetic Diseases, X-Linked / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009478:Neuropeptide Y / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D009478:Neuropeptide Y