Defects in the striatal neuropeptide Y system in X-linked dystonia-parkinsonism

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 performe...

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Bibliographic Details
Published in:Brain (London, England : 1878) England : 1878), 2013-05, Vol.136 (Pt 5), p.1555-1567
Main Authors: GOTO, Satoshi, KAWARAI, Toshitaka, MORIGAKI, Ryoma, OKITA, Shinya, KOIZUMI, Hidetaka, NAGAHIRO, Shinji, MUNOZ, Edwin L, LEE, Lillian V, KAJI, Ryuji
Format: Article
Language:English
Subjects:
Adult
Aged
Biological and medical sciences
Caudate nucleus
Corpus Striatum - metabolism
Corpus Striatum - pathology
Diseases of striated muscles. Neuromuscular diseases
Dystonic Disorders - genetics
Dystonic Disorders - metabolism
Dystonic Disorders - pathology
Female
Genetic Diseases, X-Linked - genetics
Genetic Diseases, X-Linked - metabolism
Genetic Diseases, X-Linked - pathology
Humans
Male
Medical sciences
Middle Aged
Neurology
Neuropeptide Y - biosynthesis
Neuropeptide Y - genetics
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Summary: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.
ISSN:0006-8950
1460-2156
DOI:10.1093/brain/awt084