Increased [&lt;sup&gt;3&lt;/sup&gt;H]Tiagabine Binding to GAT-1 in the Cingulate Cortex in Schizophrenia

Sundman-Eriksson, Ingrid; Blennow, Kaj; Davidsson, Pia; Dandenell, AnnaKarin; Marcusson, Jan

doi:10.1159/000048666

Cited by 11 publications

(11 citation statements)

References 26 publications

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“…Some of the genes found to have an altered expression in the present study code for proteins that have previously been associated with schizophrenia. For example, the levels of casein kinase 2 (Aksenova et al, 1991), GAD‐67 (Guidotti et al, 2000; Mirnics, et al, 2000; Costa et al, 2001), GABA transporter (Sundman‐Eriksson et al, 2002), and creatin kinase (Klushnik et al, 1991), were earlier found to be reduced in frontal cortex of schizophrenic patients, which is in agreement with the down‐regulation of the corresponding genes in MK‐801‐treated rats.…”

Section: Discussionmentioning

confidence: 99%

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Comparative genome‐ and proteome analysis of cerebral cortex from MK‐801‐treated rats

Paulson

Martin²,

Persson

et al. 2002

J of Neuroscience Research

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cDNA microarrays and two-dimensional gel-electrophoresis in combination with mass spectrometry, were used to screen alterations in mRNA and protein levels, respectively, in cerebral cortex of MK-801-treated rats. The rats were divided in two groups; group 1 (short-term treated) and group 2 (long-term treated). In group 1, four genes were up-regulated and five down-regulated. In group 2, seven genes were up-regulated and six down-regulated. In group 1, the levels of one protein was increased and eight proteins reduced. In group 2, the levels of two proteins were increased and four proteins reduced. Several of the altered genes (casein kinase 2, glutamic acid decarboxylase, synaptotagmin, gamma aminobutyric acid [GABA] transporter, creatine kinase, and cytochrome c oxidase) and proteins (superoxide dismutase, hsp 60, hsp 72 and gamma-enolase) have previously been connected to schizophrenia. Alterations of the genes (microglobulin, c-jun proto-oncogene, 40S ribosomal protein S19, adenosine diphosphate (ADP)-ribosylation factors, platelet-derived growth factor, fructose-bisphophate aldolase A, and myelin proteolipid) and the proteins (stathmin, H+-transp. Adenosine triphosphate (ATP) synthase, pyruvate dehydrogenase, beta-actin and alpha-enolase), have not, to our knowledge, earlier been implicated in schizophrenia pathology. Overall, these results with a combined approach of genomics and proteomics add to the validity of subchronic N-methyl-D-aspartate (NMDA)-receptor antagonist treatment as an animal model of schizophrenia.

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Section: Discussionmentioning

confidence: 99%

“…The level of GABA transporter 3 was up‐regulated in this study. Recently, the level of GABA transporter 1 has shown an increase in schizophrenic postmortem samples of cingulate cortex (Sundman‐Eriksson et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

Comparative genome‐ and proteome analysis of cerebral cortex from MK‐801‐treated rats

Paulson

Martin²,

Persson

et al. 2002

J of Neuroscience Research

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“…There is evidence that GABA efflux is reduced in temporal lobe sclerosis, and this could lead to a loss of inhibition during hyperexcitability [53]. GAT1 protein levels are also abnormal in the cortex of schizophrenic patients [73].…”

Section: Regulationmentioning

confidence: 99%

Synaptic uptake and beyond: the sodium- and chloride-dependent neurotransmitter transporter family SLC6

Chen

Reith

Quick

2004

Pfl�gers Archiv European Journal of Physiology

377

289

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The SLC6 family is a diverse set of transporters that mediate solute translocation across cell plasma membranes by coupling solute transport to the cotransport of sodium and chloride down their electrochemical gradients. These transporters probably have 12 transmembrane domains, with cytoplasmic N- and C-terminal tails, and at least some may function as homo-oligomers. Family members include the transporters for the inhibitory neurotransmitters GABA and glycine, the aminergic transmitters norepinephrine, serotonin, and dopamine, the osmolytes betaine and taurine, the amino acid proline, and the metabolic compound creatine. In addition, this family includes a system B(0+) cationic and neutral amino acid transporter, and two transporters for which the solutes are unknown. In general, SLC6 transporters act to regulate the level of extracellular solute concentrations. In the central and the peripheral nervous system, these transporters can regulate signaling among neurons, are the sites of action of various drugs of abuse, and naturally occurring mutations in several of these proteins are associated with a variety of neurological disorders. For example, transgenic animals lacking specific aminergic transporters show profoundly disturbed behavioral phenotypes and probably represent excellent systems for investigating psychiatric disease. SLC6 transporters are also found in many non-neural tissues, including kidney, intestine, and testis, consistent with their diverse physiological roles. Transporters in this family represent attractive therapeutic targets because they are subject to multiple forms of regulation by many different signaling cascades, and because a number of pharmacological agents have been identified that act specifically on these proteins.

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“…65 A significant increase in GABA transporter (GAT-1) binding sites was observed in the cingulate cortex of schizophrenic brains compared with controls using [3H] tiagabine labeling. 76 In a study that examined GABA tissue content, GABA A receptor a 1 subunit messenger RNA, and hGAT-1 RNA expression in the prefrontal cortex, researchers found reductions in GABA tissue content paralleled by marked increases in the cellular expression of GABA A receptor a 1 subunit and decreases in hGAT-1 mRNA. The authors concluded that their findings are consistent with reduced GABAergic transmission in the prefrontal cortex of schizophrenics.…”

Section: Genetics Of Gaba In Schizophreniamentioning

confidence: 99%

GABA and Schizophrenia: A Review of Basic Science and Clinical Studies

Wassef¹,

Baker

Kochan

2003

Journal of Clinical Psychopharmacology

223

148

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Alterations in the GABA neurotransmitter system are found in clinical and basic neuroscience schizophrenia studies as well as animal models and may be involved in the pathophysiology of schizophrenia. The interaction of GABA with other well-characterized neurotransmitter abnormalities remains to be understood. Future studies should elucidate the potential therapeutic role for GABA ligands in schizophrenia treatment.

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Increased [<sup>3</sup>H]Tiagabine Binding to GAT-1 in the Cingulate Cortex in Schizophrenia

Cited by 11 publications

References 26 publications

Comparative genome‐ and proteome analysis of cerebral cortex from MK‐801‐treated rats

Comparative genome‐ and proteome analysis of cerebral cortex from MK‐801‐treated rats

Synaptic uptake and beyond: the sodium- and chloride-dependent neurotransmitter transporter family SLC6

GABA and Schizophrenia: A Review of Basic Science and Clinical Studies

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