Reduced Labeling of Parvalbumin Neurons and Perineuronal Nets in the Dorsolateral Prefrontal Cortex of Subjects with Schizophrenia

Abstract

Alterations in cortical parvalbumin (PV)-containing neurons, including a reduced density of detectable neurons and lower PV levels, have frequently been reported in the dorsolateral prefrontal cortex (DLPFC) of schizophrenia subjects. Most PV neurons are surrounded by perineuronal nets (PNNs) and the density of PNNs, as detected by Wisteria floribunda agglutinin (WFA) labeling, has been reported to be lower in schizophrenia. However, the nature of these PNN alterations, and their relationship to disease-related changes in PV neurons, has not been assessed. Using confocal microscopy, we quantified the densities and fluorescence intensities of PV neurons and PNNs labeled with WFA or immunoreactive for the major PNN protein, aggrecan, in the DLPFC from schizophrenia and matched comparison subjects. In schizophrenia, the densities of PV cells and of PNNs were not altered; however, the fluorescence intensities of PV immunoreactivity in cell bodies and of WFA labeling and aggrecan immunoreactivity in individual PNNs around PV cells were lower. These findings indicate that the normal complements of PV cells and PNNs are preserved in schizophrenia, but the levels of PV protein and of individual PNN components, especially the carbohydrate moieties on proteoglycans to which WFA binds, are lower. Given the roles of PV neurons in regulating DLPFC microcircuits and of PNNs in regulating PV cellular physiology, the identified alterations in PV neurons and their PNNs could contribute to DLPFC dysfunction in schizophrenia.