Perineuronal nets (PNNs)

Perineuronal nets (PNNs) are specialized, lattice-like extracellular matrix structures that encapsulate the cell bodies and proximal dendrites of specific neurons, most notably parvalbumin-expressing (PV) inhibitory interneurons (Sorg et al., 2016, Chemical Reviews). Composed of a scaffold of hyaluronan, chondroitin sulfate proteoglycans (CSPGs), link proteins, and tenascin-R, PNNs act as a physical and chemical barrier that stabilizes synapses and marks the end of developmental critical periods (Pizzorusso et al., 2002, Science). By restricting structural plasticity, they maintain the stability of neural circuits but also limit the brain's ability to recover from injury or adapt to new information in adulthood. In pathological contexts, PNNs are often degraded in schizophrenia and Alzheimer's disease, contributing to cognitive dysfunction, while their persistence in spinal cord injury and PTSD prevents axonal regeneration and the extinction of traumatic memories (Berretta et al., 2015, Frontiers in Integrative Neuroscience). Therapeutic strategies targeting PNNs involve the use of enzymes like chondroitinase ABC to digest CSPGs or small molecules like 4-methylumbelliferone to inhibit their synthesis, thereby 'reopening' windows of plasticity for functional rehabilitation and memory modulation (Bradbury & Burnside, 2019, Nature Reviews Neuroscience).

Other names

Perineuronal netPNNExtracellular matrix of the brainNeuronal extracellular matrix lattice

Enzymatic degradation of chondroitin sulfate proteoglycans (CSPGs) or inhibition of hyaluronan/CSPG synthesis to reduce PNN density and restore neuroplasticity.