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Altered levels of glutamatergic receptors and Na+/K+ ATPase-alpha 1 in the prefrontal cortex of subjects with schizophrenia

Corti, C; Xuereb, JH; Crepaldi, L; Corsi, M; Michielin, F; Ferraguti, F; (2011) Altered levels of glutamatergic receptors and Na+/K+ ATPase-alpha 1 in the prefrontal cortex of subjects with schizophrenia. SCHIZOPHR RES , 128 (1-3) 7 - 14. 10.1016/j.schres.2011.01.021.

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Abstract

Evidence has accumulated over the past years that dysregulation of glutamatergic neurotransmission maybe implicated in the pathophysiology of schizophrenia. Glutamate acts on two major classes of receptors: ionotropic receptors, which are ligand-gated ion channels, and metabotropic receptors (mGluRs), coupled to heterotrimeric G-proteins. Although several pharmacological evidences point to abnormal glutamatergic transmission in schizophrenia, changes in the expression of glutamatergic receptors in the prefrontal cortex of patients with schizophrenia remains equivocal. In the present work, we have investigated glutamatergic neurotransmission in schizophrenia by assessing the expression in Brodmann Area 10 of mGluR5, the AMPA receptor subunits GluR1 and GluR2, and Na+/K+ ATPase-alpha 1, a potential modulator of glutamate uptake in the brain. Semiquantitative analysis of the expression of these proteins from postmortem brains revealed a particularly prominent reduction of GluR1 and GluR2 expression in patients with schizophrenia vs the control group. Conversely, we observed an up-regulation in the levels of Na+/K+ ATPase-alpha 1 expression. Finally, no change in the protein levels of mGluR5 was observed in schizophrenia. Our findings support and expand the hypothesis of glutamatergic dysfunction in prefrontal cortex in the pathophysiology of schizophrenia. (C) 2011 Elsevier B.V. All rights reserved.

Type: Article
Title: Altered levels of glutamatergic receptors and Na+/K+ ATPase-alpha 1 in the prefrontal cortex of subjects with schizophrenia
DOI: 10.1016/j.schres.2011.01.021
Keywords: Schizophrenia, Glutamate, AMPA, Metabotropic glutamate receptor, Prefrontal cortex, MAGNETIC-RESONANCE-SPECTROSCOPY, MESSENGER-RNA EXPRESSION, POSITIVE ALLOSTERIC MODULATOR, PREPULSE INHIBITION, LOCOMOTOR-ACTIVITY, MOLECULAR-MECHANISMS, ANTIPSYCHOTIC-DRUGS, SUBUNIT EXPRESSION, ELDERLY-PATIENTS, MGLU5 RECEPTORS
UCL classification: UCL > School of Life and Medical Sciences
UCL > School of Life and Medical Sciences > Faculty of Life Sciences
URI: http://discovery.ucl.ac.uk/id/eprint/1299724
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