title: Increased GAD67 mRNA levels are correlated with in vivo GABA synthesis in the MPTP-treated catecholamine-depleted goldfish brain.
abstract: The role of catecholamine neuronal input on GABAergic activity in the hypothalamus, telencephalon, optic tectum, and cerebellum was investigated in early recrudescent female goldfish (Carassius auratus). A new quantitative technique was developed and validated, permitting concomitant quantification and correlational analysis of glutamic acid decarboxylase 65 (GAD65), GAD67, and GAD3 mRNA levels and in vivo GABA synthesis. Catecholamine depletion was achieved by the administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP; 50 microg/g body weight) and dopamine (DA) depletion verified by HPLC. Endogenous GABA levels were increased by intraperitoneal administration of gamma-vinyl GABA (GVG; 300 microg/g body weight), an inhibitor of the GABA catabolic enzyme GABA transaminase. Treatment with MPTP resulted in a greater than twofold increase in GABA synthesis rate in the optic tectum and telencephalon. The increase in GABA synthesis rate was highly correlated with an increase in GAD67, but not GAD65 or GAD3 mRNA levels. These results suggest that catecholaminergic input exerts inhibitory effects on GABA synthesis rates through the modulation of GAD67 in the optic tectum and telencephalon. Together with previously published observations in rodents and primates, it is suggested that catecholaminergic control of GABA synthesis must have evolved more than 200 million years ago, before the emergence of the teleost fishes.
authors.affiliation: University of Ottawa Centre for Advanced Research in Environmental Genomics, Department of Biology, University of Ottawa, Ottawa, ON K1N 6N5, Canada.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Hibbert
authors.forename: Irene
authors.initials: I
authors.lastname: Fung
authors.forename: Rebecca
authors.initials: R
authors.lastname: McAuley
authors.forename: Katherine
authors.initials: K
authors.lastname: Larivière
authors.forename: Brian
authors.initials: B
authors.lastname: MacNeil
authors.forename: Nana
authors.initials: N
authors.lastname: Bafi-Yeboa
authors.forename: John
authors.initials: J
authors.lastname: Livesey
authors.forename: Vance
authors.initials: V
authors.lastname: Trudeau
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000033:anatomy & histology / Q000187:drug effects* / Q000201:enzymology; D001923:Brain Chemistry / Q000187:drug effects; D002395:Catecholamines / Q000172:deficiency*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004298:Dopamine / Q000378:metabolism; D015259:Dopamine Agents / Q000494:pharmacology*; D024202:Electrophoretic Mobility Shift Assay / Q000379:methods; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005968:Glutamate Decarboxylase / Q000235:genetics / Q000378:metabolism*; D006054:Goldfish; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors; D014018:Tissue Distribution; D014316:Tritium / Q000493:pharmacokinetics; D020888:Vigabatrin / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D002395:Catecholamines; D015259:Dopamine Agents; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D012333:RNA, Messenger; D014316:Tritium; D005680:gamma-Aminobutyric Acid; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1; C401141:glutamate decarboxylase 2; D020888:Vigabatrin; D004298:Dopamine