Glutamate decarboxylase (GAD), is a key enzyme in the central nervous system (CNS) that synthesizes the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) from glutamate. Our previous phylogenetic studies on the evolution of this enzyme indicates that there are at least two distinct forms: GAD65 and GAD67. They are the products of separate genes and probably derive from a common ancestral GAD gene following gene duplication prior to the emergence of the teleosts more than 200 Myr ago. Furthermore, a third GAD-like molecule, GAD3, discovered in the armed grenadier, Coryphaenoides (Nematonurus) armatus, is equally divergent from both GAD65 and GAD67. Specimens of C. (N.) armatus were collected by trawl at a depth of 4,000 m in the Porcupine Seabight (Northeastern Atlantic), and brains dissected and frozen for RNA extraction. All three GAD forms are found in the cerebellum, telencephalon and hypothalamus. Semiquantitative PCR analysis showed that males and females have similar levels of expression of GAD67 and GAD3 in the tissues studied. Independent of the sex examined, the levels of expression of GAD65 and GAD67 in the cerebellum were approximately half that in the telencephalon. GAD3 levels were approximately 30% higher in the cerebellum than in either the telencephalon or hypothalamus. In contrast to GAD67 and GAD3, hypothalamic expression of GAD65 mRNA is 1.8 times higher (p < 0.05) in males than in females. These data indicate that the expression of GAD65, a key enzyme for the synthesis of GABA is sexually dimorphic in females and males of C. (N.) armatus.

Anglade, I., D. Mazurais, V. Douard, V., C. Le Josic-Corcos, E.L. Mañanos, D. Michel, and O. Kah (1999) Distribution of glutamic acid decarboxylase mRNA in the forebrain of the rainbow trout as studied by in situ hybridization. J. Comp. Neurol., 410: 277–289.
Bosma, P.T., M. Blazquez, M.A. Collins, J.D.D. Bishop, G. Drouin, I.G. Priede, K. Docherty, and V.L. Trudeau (1999) Multiplicity of glutamic acid decarboxylases (GAD) in vertebrates: molecular phylogeny and evidence for a new GAD paralog. Mol. Biol. Evol., 16: 397– 404.
Bosma, P.T., M. Blazquez, E.J. Fraser, R.W. Schulz, K. Docherty, and V.L. Trudeau (2000) Sex steroid regulation of glutamate decarboxylase mRNA expression in the goldfish brain is sexually dimorphic. J. Neurochem., in press.
Brann, D.W., and V.B. Mahesh (1997) Excitatory amino acids: evidence for a role in the control of reproduction and anterior pituitary hormone secretion. Endocr. Rev., 18: 678–700.
Davis, A.M., D.R. Grattan, M. Selmanoff, and M.M. McCarthy (1996) Sex differences in glutamic acid decarboxylase mRNA in neonatal rat brain: implications for sexual differentiation. Horm. Behav., 30: 538–552.
During, M.J., K.M. Ryder, and D.D. Spencer (1995) Hippocampal GABA transporter function in temporal-lobe epilepsy. Nature, 376: 174–177.
Esclapez, M., N.J. Tillakaratne, A.J. Tobin, and C.R. Houser (1993) Comparative localization of mRNAs encoding two forms of glutamic acid decarboxylase with nonradioactive in situ hybridization methods. J. Comp. Neurol., 331: 339–362.
Finger, T.E. (1983) Organization of the teleost cerebellum. In Fish Neurobiology (ed. by R.G. Northcutt and R.E. Davis), University of Michigan Press, Ann Arbor, Mich., pp. 261– 283.
Frankfurt, M., E. Fuchs, and W. Wuttke (1984) Sex differences in gamma-aminobutyric acid and glutamate concentrations in discrete brain nuclei. Neurosci. Lett., 50: 245–250.
Fraser, E.J. (1998) The effects of season and temperature on reproductive neuroendocrine function; in particular the neurotransmitter GABA in the goldfish, Carassius auratus. PhD. Thesis, University of Aberdeen, UK.
Herbison, A.E. (1997) Estrogen regulation of GABA transmission in rat preoptic area. Brain Res. Bull., 44: 321–326.
Herbison, A.E., J.E. Robinson, and D.C. Skinner (1993) Distribution of estrogen receptor-immunoreactive cells in the preoptic area of the ewe: co-localization with glutamic acid decarboxylase but not luteinizing hormone-releasing hormone, Neuroendocrinology, 57: 751–759.
Howes, G.J. (1991) Biogeography of gadoid fishes. J. Biogeogr., 18: 596–622.
Jones, E.G., M.A. Collins, P.A. Bagley, S. Addison, and I.G. Priede (1998) The fate of cetacean carcasses in the deep sea: observations on consumption rates and succession of scavenging species in the abyssal north-east Atlantic Ocean. Proc. R. Soc. Lond. Series B, 265: 1119–1127.
Kah, O., V.L. Trudeau, B.D. Sloley, J.P. Chang, P. Dubourg, K.L. Yu, and R.E. Peter (1992) Influence of GABA on gonadotrophin release in the goldfish. Neuroendocrinology, 55: 396– 404.
Khan, I.A., and P. Thomas (1999) GABA exerts stimulatory and inhibitory influences on gonadotropin. II. Secretion in the Atlantic Croaker (Micropogonias undulatus). Neuroendocrinology, 69: 261–268.
Lüddens, H., E.R. Korpi, and P.H. Seeburg (1995) GABAA/benzodiazepine receptor heterogeneity: neurophysiological implications. Neuropharmacology, 34: 245–254.
Mañanos, E.L., I. Anglade, J. Chyb, C. Saligaut, B. Breton, and O. Kah (1999) Involvement of g aminobutyric acid in the control of GTH-1 and GTH-2 secretion in male and female rainbow trout. Neuroendocrinology, 69: 269–280.
Martin, D.L., and K. Rimvall (1993) Regulation of g-aminobutyric acid synthesis in the brain. J. Neurochem., 60: 395–407.
McCarthy, M.M. (1995) Functional significance of steroid modulation of GABAergic neurotransmission: analysis at the behavioral, cellular, and molecular levels. Horm. Behav., 29: 131– 140.
McCarthy, M.M., A.M. Davis, and J.A. Mong (1997) Excitatory neurotransmission and sexual differentiation of the brain. Brain Res. Bull., 44: 487–495.
Merrett, N.R. (1992) Demersal ichthyofaunal distribution in the abyssal eastern North Atlantic, with special reference to Coryphaenoides (Nematonurus) armatus (Macrouridae). J. Mar. Biol. Ass. UK, 72: 5–24.
Nakanishi, S. (1992) Molecular diversity of glutamate receptors and implications for brain function. Science, 258: 597–603.
Pinal, C.S., and A.J. Tobin (1998) Uniqueness and redundancy in GABA production. Perspect. Dev. Neurobiol., 5: 109–118.
Priede, I.G., P.M. Bagley, J.D. Armstrong, K.L. Smith, Jr., and N.R. Merret (1991) Direct measurement of active dispersal of food-fall by deep-sea demersal fish. Nature, 351: 647–649.
Priede, I.G., K.L. Smith, and J.D. Armstrong (1990) Foraging behaviour of abyssal grenadier fish: inferences from acoustic tagging in the north Pacific Ocean. Deep-sea Res., 37: 81– 101.
Smith, A., I.G. Priede, P.M. Bagley, and S.W. Addison (1997) Interception and dispersal of artificial food falls by scavenging fishes in the abyssal NE Atlantic: early season observations prior to annual deposition of phytodetritus. Marine Biol., 128: 329–336.
Smith, A., V.L. Trudeau, L.M. Williams, M.G. Martinoli, and I.G. Priede (1996) Melatonin receptors are present in non-optic regions of the brain of a deep-sea fish living in the absence of solar light. J. Neuroendocrinol., 8: 655–658.
Smith, K.R., Jr. (1978) Metabolism of the abyssopelagic rattail Coryphaenoides armatus measured in situ. Nature, 274: 362–364.
Soghomonian, J.J., and D.L. Martin (1998) Two isoforms of glutamate decarboxylase: why? Trends Pharmacol. Sci., 19: 500–505.
Trudeau, V.L. (1997) Neuroendocrine regulation of gonadotrophin. II. Release and gonadal growth in the goldfish, Carassius auratus. Rev. Reprod., 2: 57–68.
Trudeau, V.L., O. Kah, J.P. Chang, B.D. Sloley, P. Dubourg, E.J. Fraser, and R.E. Peter (2000a) The inhibitory effects of g-aminobutyric acid (GABA) on growth hormone secretion in the goldfish are modulated by sex steroids. J. Exp. Biol., 203: 1477–1485.
Trudeau, V.L., B.D. Sloley, and R.E. Peter (1993a) GABA stimulation of gonadotropin-II release in goldfish: involvement of GABAA receptors, dopamine, and sex steroids. Am. J. Physiol., 265: R348–R355.
Trudeau, V.L., B.D. Sloley, and R.E. Peter (1993b) Testosterone enhances GABA and taurine but not N-methyl-D,L-aspartate stimulation of gonadotropin secretion in the goldfish: possible sex steroid feedback mechanisms. J. Neuroendocrinol., 5: 129–136.
Trudeau, V.L., D. Spanswick, E.J. Fraser, K. Larivière, D. Crump, S. Chiu, M. MacMillan, and R.W. Schulz (2000b) The role of amino acid neurotransmitters in the regulation of pituitary gonadotropin release in fish. Biochem. Cell Biol., 78: 241–259.
White, B.N. (1987) Oceanic anoxic events and allopatric speciation in the deep sea. Biol. Oceanogr., 5: 243–259.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.