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Expression of parvalbumin and glutamic acid decarboxylase-67 after acute administration of MK-801. Implications for the NMDA hypofunction model of schizophrenia. Expression of parvalbumin and glutamic acid decarboxylase-67 after acute administration of MK-801. Implications for the NMDA hypofunction model of schizophrenia. Romón T., Mengod G. and Adell A. (2011) Psychopharmacology 217: 231-238. 2011-08-31T22:00:00Z<div style="text-align:justify;"></div><h3 style="line-height:1.2857;margin:0px;font-weight:bold;display:inline;text-align:justify;"><span class="ms-rteThemeForeColor-2-0 ms-rteThemeFontFace-1 ms-rteFontSize-2">Abstract</span></h3><div><h3 style="line-height:1.2857;margin:0px;color:#985735;font-weight:bold;display:inline;text-align:justify;"><br class="ms-rteThemeFontFace-1 ms-rteFontSize-2"></h3><div style="color:#000000;font-family:arial, helvetica, clean, sans-serif;text-align:justify;"><h4 style="margin:0px 0.25em 0px 0px;color:#000000;font-weight:bold;text-transform:uppercase;float:left;"><span class="ms-rteThemeFontFace-1 ms-rteFontSize-2">RATIONALE: </span></h4><p style="margin-bottom:0.5em;"><span class="ms-rteThemeFontFace-1 ms-rteFontSize-2">A reduction of GABAergic markers in postmortem tissue is consistently found in schizophrenia. This is generally mediated by a decreased expression of the calcium-binding protein, parvalbumin (PV), and the 67-kDa isoform of the GABA synthesizing enzyme glutamic acid decarboxylase (GAD(67)). Similar reductions of PV or GAD(67) are observed after repeated exposure to N-methyl-D-aspartate (NMDA) receptor antagonists but less attention has been paid to what occurs after their acute administration.</span></p><h4 style="margin:0px 0.25em 0px 0px;color:#000000;font-weight:bold;text-transform:uppercase;float:left;"><span class="ms-rteThemeFontFace-1 ms-rteFontSize-2">OBJECTIVES: </span></h4><p style="margin-bottom:0.5em;"><span class="ms-rteThemeFontFace-1 ms-rteFontSize-2">Here, we have used in situ hybridization to examine the expression of PV and GAD(67) mRNAs at 4 h and 24 h after an acute administration of MK-801 (1 mg/kg).</span></p><h4 style="margin:0px 0.25em 0px 0px;color:#000000;font-weight:bold;text-transform:uppercase;float:left;"><span class="ms-rteThemeFontFace-1 ms-rteFontSize-2">RESULTS: </span></h4><p style="margin-bottom:0.5em;"><span class="ms-rteThemeFontFace-1 ms-rteFontSize-2">Four hours after MK-801, the expression of PV mRNA decreased only in dentate gyrus of the hippocampus. Twenty four hours after this treatment, a reduction of the levels of PV mRNA was found in the medial prefrontal, orbitofrontal and entorhinal cortices, hippocampus and the basolateral nucleus of the amygdala. In contrast, no changes in the expression of GAD(67) were observed in any of the brain regions examined. Interestingly, the reduction in PV mRNA expression is observed in discrete corticolimbic subregions that have been implicated in schizophrenia, which is coincident with changes observed in postmortem tissue of schizophrenia brain.</span></p><h4 style="margin:0px 0.25em 0px 0px;color:#000000;font-weight:bold;text-transform:uppercase;float:left;"><span class="ms-rteThemeFontFace-1 ms-rteFontSize-2">CONCLUSIONS: </span></h4><p style="margin-bottom:0.5em;font-size:1.04em;"><span class="ms-rteThemeFontFace-1 ms-rteFontSize-2">These findings indicate that acute administration of a NMDA antagonist delineate a pattern of changes in GABAergic markers different from those observed in postmortem tissue in schizophrenia inasmuch as only deficits in parvalbumin (but not GAD(67)) were seen.</span><br></p></div></div><p>​<span class="ms-rteFontSize-3" style="margin:0px;padding:0px;border:0px;font-stretch:inherit;line-height:inherit;font-family:"yanone kaffeesatz";vertical-align:baseline;color:#474f51;text-align:justify;background-color:#ffffff;">[</span><a href="http://www.ncbi.nlm.nih.gov/pubmed/21465242" style="color:#ed391b;margin:0px;padding:0px;border:0px;font-stretch:inherit;font-size:18px;line-height:1.6;font-family:"yanone kaffeesatz";vertical-align:baseline;text-align:justify;background-color:#ffffff;"><span class="ms-rteFontSize-3" style="margin:0px;padding:0px;border:0px;font-style:inherit;font-stretch:inherit;line-height:inherit;font-family:inherit;vertical-align:baseline;">PubMed</span></a><span class="ms-rteFontSize-3" style="margin:0px;padding:0px;border:0px;font-stretch:inherit;line-height:inherit;font-family:"yanone kaffeesatz";vertical-align:baseline;color:#474f51;text-align:justify;background-color:#ffffff;">]</span><br></p>13

 
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Instituto de Biomedicina y Biotecnología de Cantabria.
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