Effects of quinolinic acid on messenger RNAs encoding somatostatin and glutamic acid decarboxylases in the striatum of adult rats.
The level of expression of mRNAs encoding somatostatin and two isoforms of glutamic acid decarboxylase (Mr 65,000, GAD65 and 67,000, GAD67) was examined by quantitative in situ hybridization histochemistry in the striatum of adult rats after local injections of quinolinic acid. After a 2-week survival period, Nissl strains showed a profound loss of neurons in the injected striata. With a dose of 120 nmol quinolinic acid, the lesioned area was completely devoid of somatostatin mRNA-positive neurons but contained cells expressing nicotinamide adenine dinucleotide-diaphorase activity (a marker of somatostatinergic interneurons in striatum). After 60 nmol of quinolinic acid, the number of neurons expressing somatostatin mRNA in the lesioned area was similar to controls but the level of labeling per neuron was increased. In the lesioned area, labeling for GAD65 mRNA was abolished and labeling for GAD67 mRNA markedly reduced. However, scattered neurons expressing GAD67 mRNA could still be detected. The majority of surviving GABA-ergic neurons expressed immunoreactivity to parvalbumin, a marker for striatal GABA-ergic interneurons. The results show that quinolinic acid induces dose-dependent alterations in the expression of striatal somatostatin mRNA and reveal a relative sparing of GABA-ergic interneurons in the quinolinic acid-lesioned rat striatum.
Department of Pharmacology, University of Pennsylvania, Philadelphia 19104.
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Y
Qin
J J
JJ
Soghomonian
M F
MF
Chesselet
D000110:Acetylcholinesterase / Q000032:analysis; D000818:Animals; D001345:Autoradiography; D003342:Corpus Striatum / Q000187:drug effects / Q000502:physiology*; D008058:Dihydrolipoamide Dehydrogenase / Q000032:analysis; D007839:Functional Laterality; D005968:Glutamate Decarboxylase / Q000235:genetics*; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000235:genetics*; D008297:Male; D011498:Protein Precursors / Q000235:genetics; D017378:Quinolinic Acid; D011805:Quinolinic Acids / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013004:Somatostatin / Q000235:genetics*; D013462:Sulfur Radioisotopes
D007527:Isoenzymes; D011498:Protein Precursors; D011805:Quinolinic Acids; D012333:RNA, Messenger; D013462:Sulfur Radioisotopes; D013004:Somatostatin; D008058:Dihydrolipoamide Dehydrogenase; D000110:Acetylcholinesterase; D005968:Glutamate Decarboxylase; D017378:Quinolinic Acid