Glutamatergic dysfunction in schizophrenia supported
MedWire News: Study results support a role for altered glutamatergic neurotransmission in the pathophysiology of schizophrenia.
Writing in the journal Schizophrenia Research, Francesco Ferraguti (Innsbruck Medical University, Austria) and team explain: "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."
To investigate further, the researchers studied postmortem brain tissue samples collected from 56 patients with schizophrenia and 35 mentally healthy individuals who were aged a mean of 68.0 and 65.7 years, respectively, at the time of death.
The team specifically assessed expression levels of the metabotropic receptor mGluR5, the α-amino-3-hydroxy-5-methyl-isoxazole-4-propionate (AMPA) receptor subunits GluR1 and GluR2, and Na+/K+ ATPase-α1 - a potential modulator of glutamate uptake in the brain - in Brodmann Area 10.
The researchers found that there was no significant difference between schizophrenia patients and controls regarding expression levels of mGluR5.
However, expression levels of GluR1 and GluR2 were reduced by 24% and 23%, respectively, in schizophrenia patients compared with controls.
Conversely, expression levels of Na+/K+ ATPase-α1 were increased by 17% in schizophrenia patients versus controls.
There were no significant differences in expression levels of GluR1, GluR2, mGluR5 or Na+/K+ ATPase-α1 between schizophrenia patients who had received electric shock therapy during their lives and those who had not, the researchers note.
Ferraguti and team conclude: "Our data support and expand the hypothesis of glutamatergic dysfunction in prefrontal cortex in the pathophysiology of schizophrenia; a marked reduction in the expression of AMPA receptors (GluR1 and GluR2) confirms the presence of a hypoglutamatergic tone, whereas the increase in the expression levels of Na+/K+ ATPase-α1 corroborates the view of an excessive glutamate release counteracting the reduced number/activity of ionotropic glutamatergic receptors."
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By Mark Cowen