| Abstract |
Dysfunction of prefrontal cortex (PFC) inhibitory neurons that express the calcium-binding protein parvalbumin or the neuropeptide somatostatin inschizophreniamay be related to disturbances in the migration, phenotypic specification, and/or maturation of these neurons. These pre- and postnatal developmental stages are regulated in a cell type-specific manner by various transcription factors and co-activators, fibroblast growth factor receptors (FgfR), and other molecular markers. Consequently, we used quantitative PCR to quantify mRNA levels for these developmental regulators in the PFC of 62schizophreniasubjects in whom parvalbumin and somatostatin neuron disturbances were previously reported, and in antipsychotic-exposed monkeys. Relative to unaffected comparison subjects, subjects withschizophreniaexhibited elevated mRNA levels for 1) the transcription factorMAFB, which is expressed by parvalbumin and somatostatin neurons as they migrate from the medial ganglionic eminence to the cortex, 2) the transcriptional coactivator PGC-1?, which is expressed postnatally by parvalbumin neurons to maintain parvalbumin levels and inhibitory function, and 3) FgfR1, which is required for the migration and phenotypic specification of parvalbumin and somatostatin neurons. Elevations in these markers were most prominent in youngerschizophreniasubjects and were not present in antipsychotic-exposed monkeys. Finally, expression levels of other important developmental regulators (i.e. Dlx1, Dlx5, Dlx6, SATB1, Sip1/Zeb2, ST8SIA4, cMaf, Nkx6.2, and Arx) were not altered inschizophrenia. The over-expression of a subset of molecular markers with distinct roles in the pre- and postnatal development of parvalbumin and somatostatin neurons might reflect compensatory mechanisms to sustain the development of these neurons in the face of other insults. |