Regional and subtype selective changes of neurotransmitter receptor density in a rat transgenic for the Huntington's disease mutation.

Abstract

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
• Journal: Journal of neurochemistry (J Neurochem) Vol. 94 Issue 3 Pg. 639-50 (Aug 2005) ISSN: 0022-3042 [Print] England
• PMID: 16033418 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Receptors, Neurotransmitter

Topics

• Animals
• Animals, Genetically Modified
• Autoradiography (methods)
• Brain (anatomy & histology, diagnostic imaging, metabolism)
• 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)