Two genes encode distinct glutamate decarboxylases

Erlander, Mark G.; Tillakaratne, Niranjala J.K.; Feldblum, Sophie; Patel, Nalini; Tobin, Allan J.

doi:10.1016/0896-6273(91)90077-d

Cited by 1,147 publications

(718 citation statements)

References 47 publications

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“…To confirm this phenotype in developing TH-IR neurons, we examined the coproduction of GAD by double-labeled for TH and GAD67, the isoform of GAD prevalent in somata of cortical neurons (Erlander et al, 1991;Feldblum et al, 1993;Esclapez et al, 1994). Neurons and fibers immunoreactive for GAD67 were distributed throughout the cortex as expected.…”

Section: Resultsmentioning

confidence: 73%

“…Furthermore, some cortical TH-IR neurons colocalized with GAD67, the isoform of the GABA-synthesizing enzyme most common in cortical neuron somata (Erlander et al, 1991;Feldblum et al, 1993;Esclapez et al, 1994). The intensity of GAD67 immunoreactivity in many double-labeled cell profiles was faint, suggesting that the number of cell profiles scored for TH and GAD colocalization was an underestimate.…”

Section: Discussionmentioning

confidence: 99%

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Neurochemical characterization of tyrosine hydroxylase-immunoreactive interneurons in the developing rat cerebral cortex

et al. 2008

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Understanding the development of cortical interneuron phenotypic diversity is critical because interneuron dysfunction has been implicated in several neurodevelopmental disorders. Here, tyrosine hydroxylase (TH)-immunoreactive neurons in the developing and adult rat cortex were characterized in light of findings regarding interneuron neurochemistry and development. Cortical THimmunoreactive neurons were first observed two weeks postnatally and peaked in number three weeks after birth. At subsequent ages, the number of these cell profiles was gradually reduced, and they were seen less frequently in adults. No DNA fragmentation or active caspase 3 was observed in cortical TH cells at any age examined, eliminating cell death as an explanation for the decrease in cell number. Although cortical TH cells reportedly fail to produce subsequent catecholaminergic enzymes, we found that the majority of these cells at all ages contained phosphorylated TH, suggesting that the enzyme may be active and producing L-DOPA as an end-product. Morphological criteria and colocalization of some TH cells with glutamic acid decarboxylase suggests that these cells are interneurons. Previously, parvalbumin, somatostatin, and calretinin were demonstrated in nonoverlapping subsets of interneurons. Cortical TH neurons colocalized with calretinin but not with parvalbumin or somatostatin. These findings suggest that the transitory increase in TH cell number is not due to cell death but possibly due to alterations in the amount of detectable TH present in these cells, and that at least some cortical TH-producing interneurons belong to the calretinin-containing subset of interneurons that originate developmentally in the caudal ganglionic eminence.

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Section: Resultsmentioning

confidence: 73%

Section: Discussionmentioning

confidence: 99%

Neurochemical characterization of tyrosine hydroxylase-immunoreactive interneurons in the developing rat cerebral cortex

et al. 2008

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“…15 Both GAD isoforms require pyridoxyl-5-phosphate (PLP) as a cofactor. 16 GAD65 is principally classed as an apoenzyme, which lacks PLP, whereas GAD67 is nearly always observed as a holoenzyme coupled with PLP. GAD65 is present in a membrane-associated form in the synapses, and contributes to the production of synaptic GABA.…”

Section: Discussionmentioning

confidence: 99%

Enhanced expression of glutamate decarboxylase 65 improves symptoms of rat parkinsonian models

Lee

Nam

et al. 2005

Gene Ther

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In this study, we report the amelioration of parkinsonian symptoms in rat Parkinson's disease (PD) models, as a result of the expression of glutamate decarboxylase (GAD) 65 with a modified cytomegalovirus (CMV) promoter. The transfer of the gene for gamma-amino butryic acid (GAD), the rate-limiting enzyme in gama-amino butrylic acid (GABA) production, has been investigated as a means to increase inhibitory synaptic activity. Electrophysiological evidence suggests that the transfer of the GAD65 gene to the subthalamic nucleus (STN) can change the excitatory output of this nucleus to inhibitory output. Our in vitro results also demonstrated higher GAD65 expression in cells transfected with the JDK promoter, as compared to cells transfected with the CMV promoter. Also, a rat PD model in which recombinant adeno-associated virus-2 (rAAV2)-JDK-GAD65 was delivered into the STN exhibited significant behavioral improvements, as compared to the saline-injected group. Interestingly, we observed that these behavioral improvements were more obvious in rat PD models in which rAAV2-JDK-GAD65 was injected into the STN than in rat PD models in which rAAV2-CMV-GAD65 was injected into the STN. Moreover, according to electrophysiological data, the rAAV2-JDK-GAD65-injected group exhibited more constant improvements in firing rates than did the rAAV2-CMV-GAD65-injected group. These data indicate that the JDK promoter, when coupled with GAD65 expression, is more effective with regard to parkinsonian symptoms than is the CMV promoter.

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“…GABA is synthesized from glutamate in an enzymatic reaction catalyzed by members of the glutamic acid decarboxylase (GAD) family in most, if not all GABAϩ cells. Two known molecular isoforms of GAD, GAD65 and GAD67, are coexpressed at variable ratios in GABAergic neurons (Erlander et al, 1991;Martin and Rimvall, 1993;Esclapez et al, 1994;Martin et al, 2000;Varju et al, 2001). The GAD isoforms are highly homologous at the protein level, but show different affinity to the cofactor pyridoxalphosphate (PLP) and have distinct subcellular localizations.…”

Section: Introductionmentioning

confidence: 99%

GAD isoforms exhibit distinct spatiotemporal expression patterns in the developing mouse lens: Correlation with Dlx2 and Dlx5

Kwakowsky

Schwirtlich

Zhang

et al. 2007

Developmental Dynamics

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Gamma-aminobutyric acid (GABA), the major inhibitory neurotransmitter of the adult nervous system and its biosynthetic enzyme glutamic acid decarboxylase (GAD) are abundantly expressed in the embryonic nervous system and are involved in the modulation of cell proliferation, migration, and differentiation. Here we describe for the first time the expression of GABA and embryonic and adult GAD isoforms in the developing mouse lens. We show that the GAD isoforms are sequentially induced with specific spatiotemporal profiles: GAD65 and embryonic GAD isoforms prevail in primary fibers, while GAD67 is the predominant GAD expressed in the postnatal secondary fibers. This pattern correlates well with the expression of Dlx2 and Dlx5, known as upstream regulators of GAD. GABA and GAD are most abundant at the tips of elongating fibers and are absent from organelle-free cells, suggesting their involvement is primarily in shaping of the cytoskeleton during fiber elongation stages. Developmental Dynamics 236: 3532-3544, 2007.

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Two genes encode distinct glutamate decarboxylases

Cited by 1,147 publications

References 47 publications

Neurochemical characterization of tyrosine hydroxylase-immunoreactive interneurons in the developing rat cerebral cortex

Neurochemical characterization of tyrosine hydroxylase-immunoreactive interneurons in the developing rat cerebral cortex

Enhanced expression of glutamate decarboxylase 65 improves symptoms of rat parkinsonian models

GAD isoforms exhibit distinct spatiotemporal expression patterns in the developing mouse lens: Correlation with Dlx2 and Dlx5

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