Study on effects of typical antipsychotic, haloperidol on regional cerebral blood flow with 99mTc-HMPAO SPECT in drug-naive schizophrenic patients

Abstract

Many neuropsychiatric disorders show localized dysfunction in specific cortical regions. The mechanisms underlying such region-specific vulnerabilities are unknown. Post-mortem analyses have demonstrated a selective reduction in the expression of parvalbumin (PV) in GABAergic interneurons in the frontal rather than the sensory cortex of patients with neuropsychiatric disorders such as schizophrenia, autism spectrum disorders, and bipolar disorders. PV neurons are surrounded by perineuronal nets (PNNs), and are protected from oxidative stress. Previous studies have shown that the characteristics of PNNs are brain region-specific. Therefore, we hypothesized that PV neurons and PNNs may be targeted in region-specific lesions in the brain. Oxidative stress was induced in mice by rearing them in socially isolated conditions. We systemically examined the distribution of PV neurons and PNNs in the brains of these mice as well as a control group. Our results show that the regions frequently affected in neuropsychiatric disorders show significantly lower PV expression and a lower percentage of PV neurons surrounded by PNNs in the brains of socially isolated mice. These results indicate that PV neurons and PNNs exhibit region-specific vulnerabilities. Our findings may be useful for elucidating the mechanisms underlying region-specific disruption of the brain in neuropsychiatric disorders.