The neural extracellular matrix (ECM) plays an important role in regulation of perisomatic GABAergic inhibition and synaptic plasticity in the hippocampus and cortex. Decreased labeling of perineuronal nets, a form of ECM predominantly associated with
parvalbumin-expressing interneurons in the brain, has been observed in post-mortem studies of
schizophrenia patients, specifically, in brain areas such as prefrontal cortex, entorhinal cortex, and amygdala. Moreover, glial ECM in the form of dandelion clock-like structures was reported to be altered in
schizophrenia patients. Here, we verified whether similar abnormalities in neural ECM can be reproduced in a rat model of
schizophrenia, in which animals received sub-chronic administration of
ketamine to reproduce the aspects of disease related to disrupted signaling through
N-methyl-D-aspartate receptors. Our study focused on two
schizophrenia-related brain areas, namely the medial prefrontal cortex (mPFC) and hippocampus. Semi-quantitative immunohistochemistry was performed to evaluate investigate ECM expression using
Wisteria floribunda agglutinin (WFA) and CS56 antibody, both labeling distinct
chondroitin sulfate epitopes enriched in perineuronal nets and glial ECM, respectively. Our analysis revealed that
ketamine-treated rats exhibit reduced number of WFA-labeled perineuronal nets, and a decreased intensity of
parvalbumin fluorescence in mPFC interneurons somata. Moreover, we found an increased expression of CS56 immunoreactive form of ECM. Importantly, the loss of perineuronal nets was revealed in the mPFC, and was not detected in the hippocampus, suggesting regional specificity of ECM alterations. These data open an avenue for further investigations of functional importance of ECM abnormalities in
schizophrenia as well as for search of treatments for their compensation.