Altered expression of preproenkephalin and prodynorphin mRNA in a genetic model of paroxysmal dystonia.
The dtsz mutant hamster represents a model of primary paroxysmal dystonia, in which dystonic episodes occur in response to stress. Previous examinations demonstrated striatal dysfunctions in dtsz hamsters. In the present study, in situ hybridization was used to examine preproenkephalin and prodynorphin expression as potential indices of imbalances between the striatopallidal and striatonigral pathways. Brain analyses were performed in dtsz hamsters under basal conditions, i.e., in the absence of dystonia, as well as mutant hamsters that exhibited severe stress-induced dystonic attacks immediately prior to sacrifice. In the striatum the basal expression of prodynorphin tended to be higher, while that of preproenkephalin tended to be lower in mutant hamsters in comparison to non-dystonic control hamsters. Significant basal changes were restricted to higher levels of prodynorphin in the ventrolateral striatum and lower prodynorphin and preproenkephalin mRNA expression in the hippocampus and/or in subregions of the hypothalamus. After stressful stimulation, the neuropeptides increased in several regions in both animals groups. In comparison to stimulated control hamsters, a significantly lower prodynorphin expression was found in several limbic areas of stimulated mutant hamsters during the manifestation of dystonia, while preproenkephalin mRNA was significantly lower in the anterior and dorsal striatal subregions and in nucleus accumbens. Since changes in the expression of these opioid peptides have been suggested to be related to abnormal dopaminergic activity, the present findings may reflect disturbances in striatal dopaminergic systems, and also in limbic structures in the dtsz mutant, particularly during the expression of dystonia.
Nobrega
J N
JN
Neuroimaging Research Section, Centre for Addiction and Mental Health, Toronto, Ontario, Canada, M5T 1R8.
Parkes
J H
JH
Wong
P
P
Raymond
R
R
Richter
A
A
D000704:Analysis of Variance; D000818:Animals; D001479:Basal Ganglia / Q000378:metabolism* / Q000503:physiopathology; D001921:Brain / Q000378:metabolism; D002819:Chorea / Q000235:genetics / Q000503:physiopathology; D006224:Cricetinae; D004195:Disease Models, Animal; D004421:Dystonia / Q000235:genetics* / Q000503:physiopathology; D004745:Enkephalins / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D017403:In Situ Hybridization; D009154:Mutation; D011498:Protein Precursors / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D012016:Reference Values; D014018:Tissue Distribution
D004745:Enkephalins; D011498:Protein Precursors; D012333:RNA, Messenger; C033660:preproenkephalin