Perineuronal nets and schizophrenia: the importance of neuronal coatings

Schizophrenia is a complex brain disorder associated with deficits in synaptic connectivity. The insidious onset of this illness during late adolescence and early adulthood has been reported to be dependent on several key processes of brain development including synaptic refinement, myelination and the physiological maturation of inhibitory neural networks. Interestingly, these events coincide with the appearance of perineuronal nets (PNNs), reticular structures composed of components of the extracellular matrix that coat a variety of cells in the mammalian brain. Until recently, the functions of the PNN had remained enigmatic, but are now considered to be important in development of the central nervous system, neuronal protection and synaptic plasticity, all elements which have been associated with schizophrenia. Here, we review the emerging evidence linking PNNs to schizophrenia. Future studies aimed at further elucidating the functions of PNNs will provide new insights into the pathophysiology of schizophrenia leading to the identification of novel therapeutic targets with the potential to restore normal synaptic integrity in the brain of patients afflicted by this illness.