Disease relevance of Gad1

• We report the transcriptional initiation sites and promoter sequences important for expression in islet beta-cells and C6 glioma cells, and demonstrate that the GAD67 promoter harbors elements that are responsive to glucose in primary islet cells [1].
• Cloning, characterization, and autoimmune recognition of rat islet glutamic acid decarboxylase in insulin-dependent diabetes mellitus [2].
• After sustained epileptic seizures, the markedly increased expression of glutamate decarboxylase and the reduced expression of GABA transaminase may result in increased cytoplasmic GABA concentrations in granule cells [3].
• Autoantibodies against glutamic acid decarboxylase with a higher titre and increased epitope recognition compared with those usually associated with IDDM are found in stiff-man syndrome, a rare neurological disorder characterized by a high coincidence with IDDM [4].
• We tested whether transfer of the gene coding for glutamic acid decarboxylase to dorsal root ganglion using a herpes simplex virus vector to achieve release of GABA in dorsal horn would attenuate nociception in this condition [5].

Psychiatry related information on Gad1

• Adeno-associated viral glutamate decarboxylase expression in the lateral nucleus of the rat hypothalamus reduces feeding behavior [6].
• DESIGN: Two experiments were conducted--One measured GAD67 mRNA in the barrel cortex at 3 or 6 h after a unilateral whisker cut at either light or dark onset; the other measured GAD67 mRNA after a unilateral whisker cut at light onset with or without sleep deprivation [7].
• Striatal glutamate decarboxylase messenger RNA-expressing GABAergic neurons which degenerate in Huntington's disease are not responsive to nerve growth factor [8].
• Activity-dependent regulation of glutamic acid decarboxylase in the rat barrel cortex: effects of neonatal versus adult sensory deprivation [9].
• 4 Glutamic acid decarboxylase activity was unchanged in all regions after repeated electroconvulsive shock treatment [10].

High impact information on Gad1

• Identification of the 64K autoantigen in insulin-dependent diabetes as the GABA-synthesizing enzyme glutamic acid decarboxylase [4].
• The pancreatic islet beta-cell autoantigen of relative molecular mass 64,000 (64K), which is a major target of autoantibodies associated with the development of insulin-dependent diabetes mellitus (IDDM) has been identified as glutamic acid decarboxylase, the biosynthesizing enzyme of the inhibitory neurotransmitter GABA (gamma-aminobutyric acid) [4].
• Post-mortem changes implicate adenine nucleotides and pyridoxal-5' -phosphate in regulation of brain glutamate decarboxylase [11].
• Many of the zona incerta neurons projecting to the parietal and occipital cortices could also be immunohistochemically stained with antibodies to glutamic acid decarboxylase and GABA [12].
• The loss of nigral dopamine-sensitive adenylate cyclase activity after the various brain lesions was correlated with loss of nigral glutamic acid decarboxylase but not that of tyrosine hydroxylase; nigral choline acetyltransferase was unaffected in all cases [13].

Chemical compound and disease context of Gad1

• The striatal response in animals to isolated loss of dopamine innervation is an increase in glutamate decarboxylase activity, not the decrease frequently found in the brains of patients with Parkinson's disease [14].
• 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 [15].
• The present study tested the hypothesis that estradiol reduces tissue infarction after middle cerebral artery occlusion (MCAO) in estradiol-deficient females by augmenting glutamic acid decarboxylase (GAD) expression and thus activity, leading to increases in gamma-amino-butyric acid (GABA) tissue levels [16].
• Chronic hypoxia in rats: alterations of striato-nigral angiotensin converting enzyme, GABA, and glutamic acid decarboxylase [17].
• We examined the effects of in vivo hypoxia (10% O2/90% N2) on the gamma-aminobutyric acid (GABA)/benzodiazepine receptors and on glutamic acid decarboxylase (GAD) activity in the rat brain [18].

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

• Five middle-aged (15-17 months) and five old (25-29 months) Fischer 344 x Brown Norway male rats were perfused, and coronal sections through the dorsal hippocampus were immunoreacted with antibodies either to NeuN, a neuronal marker, or to the 67-kDa isoform of glutamic acid decarboxylase (GAD), the rate-limiting enzyme for GABA synthesis [24].
• Immunohistochemical localization of GAD67-expressing neurons and processes in the rat brainstem: subregional distribution in the nucleus tractus solitarius [25].
• Overall distribution of GLYT2 mRNA-containing versus GAD67 mRNA-containing neurons and colocalization of both mRNAs in midbrain, pons, and cerebellum in rats [26].
• Areas or neuron groups expressing exclusively GLYT2 mRNA or GAD67 mRNA were rather limited, such as the superior colliculus, nucleus of the trapezoid body, and Purkinje cells [26].
• The lesion-induced increases in intraneuronal glutamate decarboxylase 67 kDa isoform (GAD67) mRNA levels on the lesion side were reversed by STN HFS in the substantia nigra, partially antagonized in the entopeduncular nucleus but unaffected in the globus pallidus [27].

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 4.1.1.15) 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

• Most of the NPY immunoreactivity induced by BDNF was colocalized with glutamate decarboxylase immunoreactivity in cultured cortical neurons [30].

Regulatory relationships of Gad1

• Most neurons within the neostriatum that intensely expressed messenger RNA for the 67,000 mol. wt isoform of glutamate decarboxylase also expressed messenger RNA for the epidermal growth factor receptor [31].
• By using in situ hybridization and immunohistochemistry, we found that 19% to 37% of glutamic acid decarboxylase (GAD) expressing neurons co-expressed GFR alpha-1 in the hippocampus [32].
• Further dual in situ hybridization studies established that approximately 60% of these high GAD67/GAT-1 cells expressed parvalbumin mRNA, a marker of one population of striatal interneurons, and had an average cross-sectional area of 152.40 microns 2 [33].
• Furthermore, all synapsin II+ terminals appear to be distinct from those expressing the GABA synthetic enzyme glutamic acid decarboxylase [34].
• Clones expressing GAD65 had higher enzymatic activity than those expressing GAD67 [35].

Other interactions of Gad1

• We analysed the presence of the neuronal nAChR subunit mRNAs alpha2-7 and beta2-4, along with the mRNA for the GABAergic markers GAD (glutamic acid decarboxylase) 65 and 67 isoforms, and VGAT (vesicular GABA transporter) in interneurons from the stratum radiatum and stratum oriens, and in CA1 pyramidal neurons [36].
• PRV immunohistochemistry combined with ISH for both GlyT2 and GAD-67 mRNAs showed that at least 63% of midline medulla GABAergic PS neurons were also glycinergic and 76% of glycinergic PS neurons were GABAergic [37].
• Our results show that BDNF does not modify levels of immunostaining for glutamic acid decarboxylase, the rate-limiting enzyme for gamma-aminobutyric acid (GABA) synthesis, and somatostatin [38].
• Neurotrophin-4/5 alone also normalized expression of messenger RNA encoding the 67 x 10(3) mol. wt isoform of glutamate decarboxylase, while none of the neurotrophins had a significant effect on preproenkephalin messenger RNA expression.(ABSTRACT TRUNCATED AT 250 WORDS)[39]
• The mRNA of GnRH in the preoptic area as well as mRNA levels of glutaminase and glutamate decarboxylase in the mediobasal hypothalamus and the preoptic area did not change during ontogeny [40].

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].

References