Perineuronal nets: Cruise from a honeycomb to the safety nets

The extracellular matrix (ECM) is a significant component of the brain, constituting up to 20 % of the brain volume and perform multifarious functions during development, maturation and regeneration of the central nervous system (CNS). ECM molecules assemble systematically to form a relatively rigid and unique lattice-like structure, known as perineuronal nets (PNNs). The PNNs usually envelop the cell body and initial axon segment and are characterized by a mesh-like structure extending along dendrites of neurons. PNNs play prominent role in the early neural development, from migration and differentiation to axonal path finding. They regulate plasticity and regeneration in adulthood by surrounding and stabilizing synaptic contacts. In this review, we have focused on the basic structure, distribution and visualization of PNNs and their role during critical periods of development, synaptogenesis and regulation of synaptic plasticity. Furthermore, we have also tried to evaluate the participation of PNNs in the pathophysiology of several brain disorders and their potential in lowering local oxidative stress. Taken together, the concepts outlined in this review emphasize the heterogeneity of PNNs in response to normal physiological and pathological conditions, highlighting the need for future studies on PNNs to target their role in etiology and potential therapeutic interventions in neurological disorders.