Expression of cholecystokinin, somatostatin, thyrotropin-releasing hormone, glutamic acid decarboxylase and tyrosine hydroxylase genes in the central nervous motor systems of the genetically dystonic hamster |
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Authors: | J-M Burgunder A Richter W Löscher |
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Institution: | (1) Laboratory of Neuromorphology, Department of Neurology and Department of Clinical Research, University of Berne, Inselspital, CH 3010 Berne, Switzerland, e-mail: jm.burgunder@dkf6.unibe.ch, CH;(2) Department of Pharmacology, Toxicology and Pharmacy, School of Veterinary Medicine, Hannover, Germany, DE |
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Abstract: | In the dt
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mutant hamster with idiopathic generalized dystonia, functional abnormalities of several neurotransmitters have been suggested
to play a role in the development of symptoms. In the present study, we have used histochemistry with 35S-ATP labeled oligonucleotides to determine whether these abnormalities are associated with modulation in the expression of
neurotransmitter genes in motor regions. We examined the expression of genes encoding cholecystokinin (CCK), somatostatin
(SRIF), thyrotropin-releasing hormone (TRH), glutamic acid decarboxylase (GAD), tyrosine hydroxylase (TH) and growth-associated
protein 43 (GAP43) in the cortex and basal ganglia of dystonic hamsters and of non-dystonic control hamsters of a related
inbred line and of a non-related outbred line. The distribution of these mRNAs in normal hamster brain was similar to that
in normal rat brain. In all cortical regions studied (frontal, parietal and piriformis), the expression of CCK was similar
in dystonic and inbred controls but was significantly greater than in outbred controls. In the anterior thalamus, CCK expression
was lower in dystonic hamsters than in both control groups. SRIF expression was significantly decreased in the cortex and
striatum of dystonic animals than in inbred and outbred control hamsters. GAD expression was lower in the striatum and substantia
nigra, pars reticulata of dystonic than in outbred hamsters, but similar values were found in all groups in the other regions
studied. TH was lower in the substantia nigra of dystonic than in inbred controls. No changes were found in GAP43 expression.
This study demonstrates that changes in modulation of the expression of some peptides and neurotransmitter enzymes can be
found in the dystonic hamster, which is in contrast to other animal models such as the dystonic rat, where no such changes
have been found. The present data are consistent with previous findings in dt
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hamsters that suggest a dysfunction within the basal ganglia-thalamocortical circuits.
Received: 29 June 1998 / Accepted: 17 May 1999 |
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Keywords: | Dystonia Neurotransmitter enzymes Golden hamster |
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