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Apr 1, 2009 (Vol. 29, No. 7)

Schizophrenia Research with Real Time PCR

  • In a technical note entitled “Quantitation of GAD67 Gene Expression in Prefrontal Cortex of Schizophrenia Patients Using the iCycler IQ™ Detection System and Molecular Beacons,” Stella Dracheva, Ph.D., of the Bronx VA Medical Center in New York, reports on a study that compared GAD67 gene expression in the dorsolateral prefrontal cortex of postmortem brain specimens from chronically ill elderly schizophrenia patients to normal controls matched for age and postmortem interval.

    According to Dr. Dracheva, research suggests that dysfunction of the dorsolateral prefrontal cortex represents one of the central features of the pathophysiology of schizophrenia. Other studies, she adds, reveal that prefrontal cortex dysfunction may be related to abnormalities in the connectivity between neurons in this region that are likely to involve GABAergic interneurons that synthesize and release the neurotransmitter GABA.

    The synthesis of GABA is catalyzed by the glutamic acid decarboxylase (GAD), which exists in two isoforms, called GAD65 and GAD67, which are the products of two independently regulated genes. GAD65 and GAD67 are coexpressed in GABAergic neurons. However, gene lesioning studies in mice suggest that GAD67 is the major isoform and is responsible for the maintenance of basal GABA levels in cells, whereas GAD65 can be rapidly activated in times of high GABA demand.

    Dr. Dracheva used real-time PCR, specifically the iCycler IQ system from Bio-Rad Laboratories, to quantitate the expression of the GAD67 gene. Her results indicated that mRNA regulation of GAD67 is significantly changed in the dorsolateral prefrontal cortex of elderly chronically ill schizophrenics.  

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