Document Detail


Regional and subtype selective changes of neurotransmitter receptor density in a rat transgenic for the Huntington's disease mutation.
MedLine Citation:
PMID:  16033418     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Huntington's disease (HD) is an autosomal dominantly inherited progressive neurodegenerative disorder caused by a CAG/polyglutamine repeat expansion in the gene encoding the huntingtin protein. We have recently generated a rat model transgenic for HD, which displays a slowly progressive phenotype resembling the human adult-onset type of disease. In this study we systematically assessed the distribution and density of 17 transmitter receptors in the brains of 2-year-old rats using quantitative multi-tracer autoradiography and high-resolution positron emission tomography. Heterozygous animals expressed increased densities of M(2) acetylcholine (increase of 148 +/- 16% of controls; p > 0.001; n = 7), nicotine (increase of 149 +/- 16% of controls; p > 0.01; n = 6), and alpha(2) noradrenergic receptors (increase of 141 +/- 15% of controls; p > 0.001; n = 6), respectively. Densities of these receptors were decreased in homozygous animals. Decreases of receptor density in both hetero- and homozygous animals were found for M1 acetylcholine, 5-HT 2A serotonin, A 2A adenosine, D1 and D2 dopamine, and GABA(A) receptors, respectively. Other investigated receptor systems showed small changes or were not affected. The present data suggest that the moderate increase of CAG/polyglutamine repeat expansions in the present rat model of Huntington's disease is characterized by subtype-selective and region-specific changes of neuroreceptor densities. In particular, there is evidence for a contribution of predominantly presynaptically localized cholinergic and noradrenergic receptors in the response to Huntington's disease pathology.
Authors:
Andreas Bauer; Karl Zilles; Andreas Matusch; Carsten Holzmann; Olaf Riess; Stephan von Hörsten
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of neurochemistry     Volume:  94     ISSN:  0022-3042     ISO Abbreviation:  J. Neurochem.     Publication Date:  2005 Aug 
Date Detail:
Created Date:  2005-07-21     Completed Date:  2005-09-19     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  2985190R     Medline TA:  J Neurochem     Country:  England    
Other Details:
Languages:  eng     Pagination:  639-50     Citation Subset:  IM    
Affiliation:
Institute of Medicine, Research Center Jülich, Jülich, Germany. an.bauer@fz-juelich.de
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MeSH Terms
Descriptor/Qualifier:
Animals
Animals, Genetically Modified
Autoradiography / methods
Brain / anatomy & histology,  metabolism*,  radionuclide imaging
Brain Mapping
Disease Models, Animal
Huntington Disease / genetics*
Image Processing, Computer-Assisted / methods
Mutation
Positron-Emission Tomography / methods
Radioligand Assay / methods
Rats
Receptors, Neurotransmitter / classification,  metabolism*
Time Factors
Trinucleotide Repeat Expansion / genetics*
Chemical
Reg. No./Substance:
0/Receptors, Neurotransmitter
Comments/Corrections
Erratum In:
J Neurochem. 2005 Aug;94(4):1167

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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