Impairments of parvalbumin-expressing GABAergic neurons (PV+ neurons) and specialized extracellular structures called perineuronal nets (PNNs) have been found in schizophrenic patients. In this study, we examined potential alterations in four subclasses of PV+ neurons colocalized with PNNs in the hippocampus of a mouse ketamine model for schizophrenia. Because biosynthesis of human natural killer-1 (HNK-1) is shown to be associated with the risk of schizophrenia, here we used mouse monoclonal Cat-315 antibody, which recognizes HNK-1 glycans on PNNs. Once-daily intraperitoneal injections of ketamine for seven consecutive days induced hyper-locomotor activity in the open field tests. The prepulse inhibition (PPI) test showed that PPI scores declined in ketamine-treated mice compared to vehicle-treated mice. The densities of PV+ neurons and Cat-315+ PNNs declined in the CA1 region of ketamine-treated mice. Interestingly, the density of Cat-315+/PV+ neurons was lower in ketamine-treated mice than in vehicle-treated mice, whereas the density of Cat-315−/PV+ neurons was not affected by ketamine. Among the four subclasses of PV+ neurons, the densities of Cat-315+/PV+ basket cells and Cat-315−/PV+ axo-axonic cells were lower in ketamine-treated mice than in vehicle-treated mice, while the densities of Cat-315−/PV+ basket cells and Cat-315+/PV+ axo-axonic cells were not affected by ketamine. Taken together, PNNs may not play a simple neuroprotective role against ketamine. Because different subclasses of PV+ neurons are considered to play distinct roles in the hippocampal neuronal network, the ketamine-induced subclass imbalance of PV+ neurons may result in abnormal network activity, which underlies the pathophysiology of schizophrenia.
All Science Journal Classification (ASJC) codes
- Psychiatry and Mental health
- Biological Psychiatry