BD, schizophrenia patients show altered neurotransmitter transporter expression
MedWire News: Results from a postmortem study show that individuals with bipolar disorder (BD) and schizophrenia have significantly altered expression of glutamate and dopamine transporters in the frontal cortex compared with mentally healthy individuals.
"Dysregulated glutamate, serotonin, and dopamine neurotransmission has been reported in BD and schizophrenia, but the underlying mechanisms of dysregulation are not clear," explain Jagadeesh Sridhara Rao and colleagues from the National Institutes of Health in Bethesda, Maryland, USA.
To investigate whether this dysregulation is associated with alterations in expression of serotonin reuptake transporter (SERT), dopamine reuptake transporter (DAT), and excitatory amino acid transporters (EAATs 1-4), the team studied postmortem frontal cortex samples from 10 BD patients, 10 schizophrenia patients, and 10 age-matched mentally healthy controls.
There were no significant differences among the groups regarding mean age at time of death, postmortem interval, and brain pH, the researchers note in the Journal of Affective Disorders.
The team found that mean EAAT1 protein levels were increased by a significant 78% and 129% in BD and schizophrenia patients, respectively, compared with controls. Mean EAAT1 mRNA levels were also a significant 3.69- and 3.83-fold higher in BD and schizophrenia patients, respectively, compared with controls.
Mean EAAT2 protein levels were 37% lower in BD patients compared with controls, with no significant difference between schizophrenia patients and controls. Accordingly, mean EAAT2 mRNA levels were lower BD patients than controls, but were not reduced in schizophrenia patients.
Mean postsynaptic EAAT3 and EAAT4 protein levels were a respective 126% and 136% higher in schizophrenia patients compared with controls, with corresponding 3.48-and 3.40-fold increases in mRNA levels. There were no significant differences between BD patients and controls regarding EAAT3 and EAAT4 protein and mRNA levels.
DAT protein levels were reduced by a significant 31% and 27% in BD and schizophrenia patients compared with controls.
However, there were no significant differences among the groups regarding presynaptic SERT protein levels.
Lifetime medication use, age and other variables did not significantly affect the findings, the researchers note.
Rao and team conclude: "Our findings of abnormal mRNA and protein levels of reuptake transporters for dopamine and glutamate suggest that these changes play important roles in the imbalanced dopamine and glutamate neurotransmission in both BD and schizophrenia.
"Further study of the effects of EAATs on N-methyl-d-aspartate function in BD and schizophrenia could elucidate the disease pathologies and help to develop glutamate neurotransmitter modulators of therapeutic use."
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By Mark Cowen