DLX-1 mRNA expression in the dorsolateral prefrontal cortex of schizophrenic patients and controls
M. Molnar; W. E. Bunney; E. E. Jones
Society for Neuroscience annual meeting. 2005.
Reduced expression of GABAergic markers, including the 67 KD form of glutamic acid decarboxylase (GAD-67), in the dorsolateral prefrontal cortex (DLPFC) is the most robust and consistent finding in postmortem studies of schizophrenia. This reduction has been observed restricted to a specific subset of GABAergic neurons, while all remaining interneurons express normal levels of GABA markers. These findings may be interpreted as the result of decreased cortical activity in the DLPFC based on defective circuitry. Alternatively, we can hypothesize that the reduced expression of GAD-67 is a result of abnormalities in the expression of genes regulating the maturation of the GABAergic phenotype. In this regard, the Distal-less (DLX) genes represent good candidates for the study of schizophrenia, as they play a fundamental role in the maturation of cortical GABAergic phenotype. In fact, ectopic expression of members of the DLX gene family is sufficient to induce expression of GAD-67. DLX genes are expressed in specific sequential order during early development. Thereafter, DLX-1 and DLX-5 expression persists in adult GABAergic neurons. In the present study we analyzed the expression of DLX-1 in the adult human dorsolateral prefrontal cortex (Brodmann area 9) using quantitative in situ hybridization. DLX-1 mRNA is expressed in the adult human cortex, with highest expression in layers II and IV. In a second phase of this study, we quantified and compared the level of expression of DLX-1 mRNA in cortical area 9 of schizophrenic patients and controls.