The parafascicular thalamic nucleus modulates messenger RNA encoding glutamate decarboxylase 67 in rat striatum.
We investigated whether the parafascicular thalamostriatal pathway, one of the major excitatory inputs to the striatum, regulates the expression in rat striatum of messenger RNA encoding two isoforms of glutamate decarboxylase (mol. wt 67,000: glutamate decarboxylase 67 and mol. wt 65,000: glutamate decarboxylase 65). Acute (one day) and chronic (14 days) electrolytic lesions of the parafascicular nucleus resulted in 58% and 23% decreases in glutamate decarboxylase 67 messenger RNA expression, respectively, as determined by northern blot analysis. Glutamate decarboxylase 65 messenger RNA was not modified by either lesion. Sections of sham- and acute-lesioned striata were processed for in situ hybridization histochemistry at the single cell level with an RNA probe for glutamate decarboxylase 67. Labelling of glutamate decarboxylase 67 messenger RNA was decreased in both types of cells known to be present in the striatum, i.e. the lightly and the very densely-labelled neurons. The frequency distribution of glutamate decarboxylase 67 labelling per neuron in the lesioned striata, in fact, was shifted to the left and its median was lower than in the sham-lesioned striata. In view of the excitatory nature of the thalamostriatal pathway, we examined the subtype of glutamate receptors modulating the glutamate decarboxylase 67 gene expression. The N-methyl-D-aspartate-type receptor antagonist, dizocilpine, at 0.1-0.5 mg/kg i.p., produced a marked and persistent reduction in striatal glutamate decarboxylase 67 messenger RNA. The non-N-methyl-D-aspartate receptor antagonist, 6,7-dinitroquinoxaline-2,3-dione (12 nmol/side, i.c.v.) had no such effect. The results provide evidence that excitatory thalamostriatal afferents selectively modulate the gene expression of glutamate decarboxylase 67, probably through the N-methyl-D-aspartate subtype of glutamate receptors.
Giorgi
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S
Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
Rimoldi
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M
Rossi
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A
Consolo
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S
D000818:Animals; D001931:Brain Mapping; D003342:Corpus Striatum / Q000201:enzymology*; D018076:DNA, Complementary; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004572:Electrolysis; D005968:Glutamate Decarboxylase / Q000096:biosynthesis*; D017403:In Situ Hybridization; D007527:Isoenzymes / Q000096:biosynthesis*; D008297:Male; D009474:Neurons / Q000201:enzymology*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D013787:Thalamic Nuclei / Q000502:physiology*; D014158:Transcription, Genetic / Q000187:drug effects
D018076:DNA, Complementary; D007527:Isoenzymes; D012333:RNA, Messenger; D016291:Dizocilpine Maleate; D005968:Glutamate Decarboxylase