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Gene Review

Gad1  -  glutamate decarboxylase 1

Rattus norvegicus

Synonyms: 67 kDa glutamic acid decarboxylase, GAD-67, Gad67, Glutamate decarboxylase 1, Glutamate decarboxylase 67 kDa isoform
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Disease relevance of Gad1


Psychiatry related information on Gad1


High impact information on Gad1


Chemical compound and disease context of Gad1


Biological context of Gad1

  • Glutamic acid decarboxylase 67 (GAD67) gene expression in discrete regions of the rostral preoptic area change during the oestrous cycle and with age [19].
  • The brain contains two forms of the GABA synthetic enzyme glutamate decarboxylase (GAD), which differ in molecular size, amino acid sequence, antigenicity, cellular and subcellular location, and interaction with the GAD cofactor pyridoxal phosphate [20].
  • Chronic stress-induced increases in GAD65 mRNA expression predict enhanced availability of GAD65 apoenzyme after prolonged stimulation, whereas acute stress-specific GAD67 upregulation is consistent with de novo synthesis of active enzyme by discrete stressful stimuli [21].
  • GAD65 and GAD67 mRNAs were detected at E11 and increased exponentially over three orders of magnitude during embryonic development, then declined approximately threefold in the first-2 postnatal weeks [22].
  • Brain L-glutamate decarboxylase. Inhibition by phosphorylation and activation by dephosphorylation [23].

Anatomical context of Gad1


Associations of Gad1 with chemical compounds

  • GABA-C receptor subunits (rho1, rho2, rho3) and GABA synthesizing enzymes (GAD 65 and GAD 67) were shown to be expressed as assayed by RT-PCR, and GABA-C receptor stimulation by CACA obviously increased intracellular Ca2+ concentration in the anterior pituitary cells [28].
  • GAD65 and GAD67 are two isoforms of the enzyme glutamic acid decarboxylase which catalyze the production of GABA from glutamate, primarily in the brain [1].
  • Characterization of the rat GAD67 gene promoter reveals elements important for basal transcription and glucose responsiveness [1].
  • Autoantibodies against the 64-kDa protein were recently shown to immunoprecipitate glutamic acid decarboxylase (GAD; L-glutamate 1-carboxy-lyase, EC from brain and from islets [2].
  • l-Glutamic acid decarboxylase (GAD) exists as both membrane-associated and soluble forms in the mammalian brain [29].

Co-localisations of Gad1


Regulatory relationships of Gad1


Other interactions of Gad1


Analytical, diagnostic and therapeutic context of Gad1

  • To evaluate GAD67 mRNA in striatonigral and striatopallidal neurons, identified as enkephalin (-) and (+) neurons, double-labelling in situ hybridization was used [41].
  • Our findings support the use of immunohistochemistry for GAD67 as a marker for the localization of GABAergic cells and terminal processes in the rat brainstem [25].
  • The staining combinations employed the immunoperoxidase method, with different chromogens for distinguishing the motilin-like immunoreactivity from glutamic acid decarboxylase immunoreactivity by different colors, or the immunoperoxidase method for one antiserum and immunofluorescence for the other [42].
  • Immunocytochemical staining of the cultures showed the presence of a large number of glutamic acid decarboxylase-containing neurons, and electrical stimulation of randomly selected neurons produced in many cases chloride-mediated and bicuculline-sensitive inhibitory synaptic currents in postsynaptic cells [43].
  • Cellular sites of GAT-1, GAD67, and parvalbumin mRNAs were visualized using a combination of radioactive and alkaline phosphatase-labeled oligonucleotides and emulsion autoradiography; GAD67 immunoreactivity was detected using a polyclonal antibody (K2) and 3'3"-diaminobenzidine [33].


  1. Characterization of the rat GAD67 gene promoter reveals elements important for basal transcription and glucose responsiveness. Pedersen, A.A., Videbaek, N., Skak, K., Petersen, H.V., Michelsen, B.K. DNA Seq. (2001) [Pubmed]
  2. Cloning, characterization, and autoimmune recognition of rat islet glutamic acid decarboxylase in insulin-dependent diabetes mellitus. Michelsen, B.K., Petersen, J.S., Boel, E., Møldrup, A., Dyrberg, T., Madsen, O.D. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
  3. Expression of plasma membrane GABA transporters but not of the vesicular GABA transporter in dentate granule cells after kainic acid seizures. Sperk, G., Schwarzer, C., Heilman, J., Furtinger, S., Reimer, R.J., Edwards, R.H., Nelson, N. Hippocampus. (2003) [Pubmed]
  4. Identification of the 64K autoantigen in insulin-dependent diabetes as the GABA-synthesizing enzyme glutamic acid decarboxylase. Baekkeskov, S., Aanstoot, H.J., Christgau, S., Reetz, A., Solimena, M., Cascalho, M., Folli, F., Richter-Olesen, H., De Camilli, P., Camilli, P.D. Nature (1990) [Pubmed]
  5. Gene transfer of glutamic acid decarboxylase reduces neuropathic pain. Hao, S., Mata, M., Wolfe, D., Huang, S., Glorioso, J.C., Fink, D.J. Ann. Neurol. (2005) [Pubmed]
  6. Adeno-associated viral glutamate decarboxylase expression in the lateral nucleus of the rat hypothalamus reduces feeding behavior. Noordmans, A.J., Song, D.K., Noordmans, C.J., Garrity-Moses, M., During, M.J., Fitzsimons, H.L., Imperiale, M.J., Boulis, N.M. Gene Ther. (2004) [Pubmed]
  7. Sleep modifies glutamate decarboxylase mRNA within the barrel cortex of rats after a mystacial whisker trim. Churchill, L., Taishi, P., Guan, Z., Chen, L., Fang, J., Krueger, J.M. Sleep. (2001) [Pubmed]
  8. Intrastriatal infusion of nerve growth factor after quinolinic acid prevents reduction of cellular expression of choline acetyltransferase messenger RNA and trkA messenger RNA, but not glutamate decarboxylase messenger RNA. Venero, J.L., Beck, K.D., Hefti, F. Neuroscience (1994) [Pubmed]
  9. Activity-dependent regulation of glutamic acid decarboxylase in the rat barrel cortex: effects of neonatal versus adult sensory deprivation. Akhtar, N.D., Land, P.W. J. Comp. Neurol. (1991) [Pubmed]
  10. The effect of repeated electroconvulsive shock on GABA synthesis and release in regions of rat brain. Green, A.R., Vincent, N.D. Br. J. Pharmacol. (1987) [Pubmed]
  11. Post-mortem changes implicate adenine nucleotides and pyridoxal-5' -phosphate in regulation of brain glutamate decarboxylase. Miller, L.P., Walters, J.R., Martin, D.L. Nature (1977) [Pubmed]
  12. A major direct GABAergic pathway from zona incerta to neocortex. Lin, C.S., Nicolelis, M.A., Schneider, J.S., Chapin, J.K. Science (1990) [Pubmed]
  13. Localization of nigral dopamine-sensitive adenylate cyclase on neurons originating from the corpus striatum. Spano, P.F., Trabucchi, M., Di Chiara, G. Science (1977) [Pubmed]
  14. Striatal dopamine depletion, dopamine receptor stimulation, and GABA metabolism: implications for the therapy of Parkinson's disease. Bennett, J.P. Ann. Neurol. (1986) [Pubmed]
  15. Differential and time-dependent changes in gene expression for type II calcium/calmodulin-dependent protein kinase, 67 kDa glutamic acid decarboxylase, and glutamate receptor subunits in tetanus toxin-induced focal epilepsy. Liang, F., Jones, E.G. J. Neurosci. (1997) [Pubmed]
  16. Estradiol alters only GAD(67) mRNA levels in ischemic rat brain with no consequent effects on GABA. Joh, H.D., Searles, R.V., Selmanoff, M., Alkayed, N.J., Koehler, R.C., Hurn, P.D., Murphy, S.J. J. Cereb. Blood Flow Metab. (2006) [Pubmed]
  17. Chronic hypoxia in rats: alterations of striato-nigral angiotensin converting enzyme, GABA, and glutamic acid decarboxylase. Arregui, A., Barer, G.R. J. Neurochem. (1980) [Pubmed]
  18. Increased binding of [3H]muscimol and [3H]flunitrazepam in the rat brain under hypoxia. Ninomiya, H., Taniguchi, T., Kameyama, M., Fujiwara, M. J. Neurochem. (1988) [Pubmed]
  19. Glutamic acid decarboxylase 67 (GAD67) gene expression in discrete regions of the rostral preoptic area change during the oestrous cycle and with age. Cashion, A.B., Smith, M.J., Wise, P.M. J. Neuroendocrinol. (2004) [Pubmed]
  20. Two genes encode distinct glutamate decarboxylases. Erlander, M.G., Tillakaratne, N.J., Feldblum, S., Patel, N., Tobin, A.J. Neuron (1991) [Pubmed]
  21. Region-specific regulation of glutamic acid decarboxylase (GAD) mRNA expression in central stress circuits. Bowers, G., Cullinan, W.E., Herman, J.P. J. Neurosci. (1998) [Pubmed]
  22. Developmental kinetics of GAD family mRNAs parallel neurogenesis in the rat spinal cord. Somogyi, R., Wen, X., Ma, W., Barker, J.L. J. Neurosci. (1995) [Pubmed]
  23. Brain L-glutamate decarboxylase. Inhibition by phosphorylation and activation by dephosphorylation. Bao, J., Cheung, W.Y., Wu, J.Y. J. Biol. Chem. (1995) [Pubmed]
  24. Stereological quantification of GAD-67-immunoreactive neurons and boutons in the hippocampus of middle-aged and old Fischer 344 x Brown Norway rats. Shi, L., Argenta, A.E., Winseck, A.K., Brunso-Bechtold, J.K. J. Comp. Neurol. (2004) [Pubmed]
  25. Immunohistochemical localization of GAD67-expressing neurons and processes in the rat brainstem: subregional distribution in the nucleus tractus solitarius. Fong, A.Y., Stornetta, R.L., Foley, C.M., Potts, J.T. J. Comp. Neurol. (2005) [Pubmed]
  26. Overall distribution of GLYT2 mRNA-containing versus GAD67 mRNA-containing neurons and colocalization of both mRNAs in midbrain, pons, and cerebellum in rats. Tanaka, I., Ezure, K. Neurosci. Res. (2004) [Pubmed]
  27. High-frequency stimulation of the subthalamic nucleus selectively reverses dopamine denervation-induced cellular defects in the output structures of the basal ganglia in the rat. Salin, P., Manrique, C., Forni, C., Kerkerian-Le Goff, L. J. Neurosci. (2002) [Pubmed]
  28. Gamma-aminobutyric acid (GABA)-C receptor stimulation increases prolactin (PRL) secretion in cultured rat anterior pituitary cells. Nakayama, Y., Hattori, N., Otani, H., Inagaki, C. Biochem. Pharmacol. (2006) [Pubmed]
  29. Demonstration of functional coupling between gamma -aminobutyric acid (GABA) synthesis and vesicular GABA transport into synaptic vesicles. Jin, H., Wu, H., Osterhaus, G., Wei, J., Davis, K., Sha, D., Floor, E., Hsu, C.C., Kopke, R.D., Wu, J.Y. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  30. Regulation of neuropeptide expression in cultured cerebral cortical neurons by brain-derived neurotrophic factor. Nawa, H., Bessho, Y., Carnahan, J., Nakanishi, S., Mizuno, K. J. Neurochem. (1993) [Pubmed]
  31. A subpopulation of striatal gabaergic neurons expresses the epidermal growth factor receptor. Kornblum, H.I., Gall, C.M., Seroogy, K.B., Lauterborn, J.C. Neuroscience (1995) [Pubmed]
  32. GFR alpha-1 is expressed in parvalbumin GABAergic neurons in the hippocampus. Sarabi, A., Hoffer, B.J., Olson, L., Morales, M. Brain Res. (2000) [Pubmed]
  33. Localization of GAT-1 GABA transporter mRNA in rat striatum: cellular coexpression with GAD67 mRNA, GAD67 immunoreactivity, and parvalbumin mRNA. Augood, S.J., Herbison, A.E., Emson, P.C. J. Neurosci. (1995) [Pubmed]
  34. Differential expression of synapsins I and II among rat retinal synapses. Mandell, J.W., Czernik, A.J., De Camilli, P., Greengard, P., Townes-Anderson, E. J. Neurosci. (1992) [Pubmed]
  35. Rat-1 fibroblasts engineered with GAD65 and GAD67 cDNAs in retroviral vectors produce and release GABA. Ruppert, C., Sandrasagra, A., Anton, B., Evans, C., Schweitzer, E.S., Tobin, A.J. J. Neurochem. (1993) [Pubmed]
  36. Functional and molecular characterization of neuronal nicotinic ACh receptors in rat CA1 hippocampal neurons. Sudweeks, S.N., Yakel, J.L. J. Physiol. (Lond.) (2000) [Pubmed]
  37. GABAergic and glycinergic presympathetic neurons of rat medulla oblongata identified by retrograde transport of pseudorabies virus and in situ hybridization. Stornetta, R.L., McQuiston, T.J., Guyenet, P.G. J. Comp. Neurol. (2004) [Pubmed]
  38. Overexpression of neuropeptide Y induced by brain-derived neurotrophic factor in the rat hippocampus is long lasting. Reibel, S., Vivien-Roels, B., Lê, B.T., Larmet, Y., Carnahan, J., Marescaux, C., Depaulis, A. Eur. J. Neurosci. (2000) [Pubmed]
  39. Brain-derived neurotrophic factor and neurotrophin-4/5 modify neurotransmitter-related gene expression in the 6-hydroxydopamine-lesioned rat striatum. Sauer, H., Wong, V., Björklund, A. Neuroscience (1995) [Pubmed]
  40. Ontogeny of the GNRH-, glutaminase- and glutamate decarboxylase-gene expression in the hypothalamus of female rats. Roth, C., Leonhardt, S., Theiling, K., Lakomek, M., Jarry, H., Wuttke, W. Brain Res. Dev. Brain Res. (1998) [Pubmed]
  41. Selective modifications in GAD67 mRNA levels in striatonigral and striatopallidal pathways correlate to dopamine agonist priming in 6-hydroxydopamine-lesioned rats. Carta, A.R., Fenu, S., Pala, P., Tronci, E., Morelli, M. Eur. J. Neurosci. (2003) [Pubmed]
  42. Chemical heterogeneity in cerebellar Purkinje cells: existence and coexistence of glutamic acid decarboxylase-like and motilin-like immunoreactivities. Chan-Palay, V., Nilaver, G., Palay, S.L., Beinfeld, M.C., Zimmerman, E.A., Wu, J.Y., O'Donohue, T.L. Proc. Natl. Acad. Sci. U.S.A. (1981) [Pubmed]
  43. Modulation of gamma-aminobutyric acid-mediated inhibitory synaptic currents in dissociated cortical cell cultures. Vicini, S., Alho, H., Costa, E., Mienville, J.M., Santi, M.R., Vaccarino, F.M. Proc. Natl. Acad. Sci. U.S.A. (1986) [Pubmed]
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