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Reduced Labeling of Parvalbumin Neurons and Perineuronal Nets in the Dorsolateral Prefrontal Cortex of Subjects with Schizophrenia
Enwright JF, Sanapala S, Foglio A, Berry R, Fish KN and Lewis DA
Neuropsychopharmacology, Published online, 2016

Alterations in cortical parvalbumin (PV)-containing neurons have frequently been reported in the dorsolateral prefrontal cortex (DLPFC) of schizophrenia subjects. These alterations include several reports of lower levels of PV mRNA and protein, and mixed reports of changes in PV cell density. 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. 

Dr. John Enwright and colleagues in the Translational Neuroscience Program used confocal microscopy to examine the densities and quantify the fluorescent-labeling intensities of PV neurons and PNNs detected with WFA or immunoreactive for the major PNN protein, aggrecan, in the DLPFC from schizophrenia and matched comparison subjects.  They found that in schizophrenia, the densities of PV cells and of PNNs were not altered; however, the 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 the 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.  

Contributors:
John F. Enwright III, PhD, Kenneth N. Fish, PhD and David A. Lewis, MD (Department of Psychiatry, University of Pittsburgh)

Sowmya Sanapala, BS, Aaron Foglio, BS and Raissa Berry, BS (Department of Neuroscience, University of Pittsburgh)

This article appears in the journal Neuropsychopharmacology.  To view the abstract, click here.