title: Altered levels of glutamatergic receptors and Na+/K+ ATPase-α1 in the prefrontal cortex of subjects with schizophrenia.
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-α1, 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-α1 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.
authors.affiliation: Dept. Biology, Psychiatry Centre of Excellence in Drug Discovery, GlaxoSmithKline Medicines Research Centre, Verona, Italy.
authors.forename: Corrado
authors.initials: C
authors.lastname: Corti
authors.forename: John Henry
authors.initials: JH
authors.lastname: Xuereb
authors.forename: Luca
authors.initials: L
authors.lastname: Crepaldi
authors.forename: Mauro
authors.initials: M
authors.lastname: Corsi
authors.forename: Francesca
authors.initials: F
authors.lastname: Michielin
authors.forename: Francesco
authors.initials: F
authors.lastname: Ferraguti
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011180:Postmortem Changes; D017397:Prefrontal Cortex / Q000378:metabolism*; D017470:Receptors, Glutamate / Q000145:classification / Q000378:metabolism*; D012559:Schizophrenia / Q000473:pathology*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D018709:Statistics, Nonparametric
chemical_list: D017470:Receptors, Glutamate; D000254:Sodium-Potassium-Exchanging ATPase