TBR1 mRNA EXPRESSION IS DOWREGULATED IN THE DORSOLATERAL PREFRONTAL CORTEX OF SCHIZOPHRENICS.
M. Molnar; W.E.Bunney; E.G.Jones
Society for Neuroscience 33rd Annual Meeting. 2003.
Dysfunction of the prefrontal cortex is believed to be a central feature underlying the cognitive abnormalities observed in schizophrenic patients. This dysfunction may be related to alterations in glutamatergic or gamma aminobutyric acid neurotransmission based on defective cortical connectivity. T-brain-1(Tbr1) is a transcription factor mainly expressed in glutamatergic cortical neurons during early development. Studies in rodents show that disruption of Tbr-1 expression leads to profound alterations of cortico-cortical and cortico-thalamic connectivity. In the present study we investigated the expression of Tbr-1 mRNA in the dorsolateral prefrontal cortex of schizophrenic patients compared to matched controls. We found a trend toward reduced expression of Tbr-1 mRNA in all layers, and a statistically significant reduction in layer III, IV and V whose cells are the main sources of cortico-cortical, thalamo-cortical and cortico-thalamic connections. Our data suggest an involvement of this transcription factor in the pathophysiology of schizophrenia, and that the glutamatergic neurons of the prefrontal cortex are potentially affected with consequences for cortical integration. Support Contributed By: Grant numbers MH54844 and MH60398 from0 NIMH, and by the Pritzker Neuropsychiatric Disorders Research Consortium. M. Molnar was the recipient of a Young Investigator Award from NARSAD.