This title appears in the Scientific Report :
2005
Please use the identifier:
http://dx.doi.org/10.1111/j.1471-4159.2005.03169.x in citations.
Regional and subtype selective changes of neurotransmitter receptor density in a rat transgenic for the Huntington's disease mutation
Regional and subtype selective changes of neurotransmitter receptor density in a rat transgenic for the Huntington's disease mutation
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 phenoty...
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Personal Name(s): | Bauer, A. |
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Zilles, K. / Matusch, A. / Holzmann, C. / Riess, O. / von Hörsten, S. | |
Contributing Institute: |
Institut für Medizin; IME |
Published in: | Journal of neurochemistry, 94 (2005) S. 639 - 650 |
Imprint: |
Oxford
Wiley-Blackwell
2005
|
Physical Description: |
639 - 650 |
PubMed ID: |
16033418 |
DOI: |
10.1111/j.1471-4159.2005.03169.x |
Document Type: |
Journal Article |
Research Program: |
Neurowissenschaften |
Series Title: |
Journal of Neurochemistry
94 |
Subject (ZB): | |
Publikationsportal JuSER |
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. |