Region-specific and Age-related Decrease of Parvalbumin Gene Expression in the Prefrontal Cortex of Elderly Patients with Schizophrenia

Background: Multiple studies on schizophrenia have suggested a dysfunction of γ-aminobutyric acid (GABA) transmission in the prefrontal cortex (PFC) and some vulnerability of the central nervous system to the aging process. Since one of the calcium-binding proteins, parvalbumin (PV) is a useful marker for a subpopulation of GABAergic local circuit neurons, we determined the PV gene expression in the PFC in schizophrenic brains to study a possible involvement of GABAergic system and its vulnerability, if any, to the aging process. Methods: We attempted a detailed in situ hybridization to determine the PV gene expression throughout the three PFC subregions (Brodmann areas; BAs 9, 10, and 11) from six elderly patients with schizophrenia and five age-matched normal individuals. Results: The regional levels of PV messenger RNA (mRNA) were significantly decreased in BAs 9 and 10 of schizophrenics compared with controls. The cellular levels were significantly decreased in layers III, IV, and V in BAs 9 and 10 of schizophrenics. However, in BA 11 of schizophrenics, the cellular level was significantly decreased in layer in alone. There were significant reverse correlations between the PV mRNA levels in those areas and the age at death in the schizophrenic group, but not in the controls. Conclusion: The present results not only provide further evidence of a disturbance in GABA transmission in the PFC of schizophrenics, but also suggest that such dysfunction may be region-specific and vulnerable to the aging process.