| 1 | 我精神病学2012 169年10月:1082-91 |
|---|---|
| PMID | 22983435 |
| Title | Deficits in transcriptional regulators of cortical parvalbumin neurons in schizophrenia. |
| Abstract | Inschizophrenia, alterations within the prefrontal cortical GABA system appear to be most prominent in neurons that contain parvalbumin or somatostatin but not calretinin. The transcription factors Lhx6 andSOX6play critical roles in the specification, migration, and maturation of parvalbumin and somatostatin neurons, but not calretinin neurons, and continue to be strongly expressed in this cell type-specific manner in the prefrontal cortex of adult humans. The authors investigated whether Lhx6 and/orSOX6mRNA levels are deficient inschizophrenia, which may contribute to cell type-specific disturbances in cortical parvalbumin and somatostatin neurons. The authors used quantitative PCR and in situ hybridization with film and grain counting analyses to quantify mRNA levels in postmortem samples of prefrontal cortex area 9 of 42schizophreniasubjects and 42 comparison subjects who had no psychiatric diagnoses in life, as well as antipsychotic-exposed monkeys. Inschizophreniasubjects, the authors observed lower mRNA levels for Lhx6, parvalbumin, somatostatin, and glutamate decarboxylase (GAD67; the principal enzyme in GABA synthesis), but notSOX6or calretinin. Cluster analysis revealed that a subset ofschizophreniasubjects consistently showed the most severe deficits in the affected transcripts. Grain counting analyses revealed that some neurons that normally express Lhx6 were not detectable inschizophreniasubjects. Finally, lower Lhx6 mRNA levels were not attributable to psychotropic medications or illness chronicity. These data suggest that in a subset of individuals withschizophrenia, Lhx6 deficits may contribute to a failure of some cortical parvalbumin and somatostatin neurons to successfully migrate or develop a detectable GABA-ergic phenotype. |
| SCZ Keywords | schizophrenia |