Perineuronal nets (PNNs) are special structures surrounding certain neurones in the central nervous system. They play a crucial role in protecting neurones and regulating their activity.
PNNs are made up of complex extracellular matrix molecules (molecules outside of cells), including chondroitin sulphate proteoglycans (CSPGs) and hyaluronan. They surround the cell bodies, dendrites, and axons of certain types of neurones, forming a dense and stable lattice-like structure.
The primary function of PNNs is to modulate synaptic plasticity, which is the ability of neurones to change the strength of their connections in response to experience. PNNs regulate the activity of enzymes that break down CSPGs, which can limit the ability of neurones to form new synapses or modify existing ones.
PNNs are also involved in regulating the activity of neurotransmitters like gamma-aminobutyric acid (GABA) and glutamate, which are involved in inhibiting and exciting neurones, respectively. They selectively bind to and release these neurotransmitters, modulating their activity and influencing the overall excitability of neural circuits.
Abnormalities in PNNs have been linked to a variety of brain disorders, including schizophrenia, epilepsy, and Alzheimer’s disease. In schizophrenia, abnormalities in PNNs have been observed in the prefrontal cortex, a brain region involved in higher cognitive functions. In epilepsy, PNNs limit the spread of seizures by stabilising neural circuits, but they may also contribute to the development of epilepsy by limiting the ability of neurones to form new synapses. In Alzheimer’s disease, PNNs accumulate around amyloid beta plaques, which are a hallmark of the disease.
Further research is needed to fully understand the role of PNNs in the brain and their implications for brain health and disease. Manipulation of PNNs with drugs has the potential to enhance plasticity in the brain and provide treatment options for neurological disorders.
Figure. PNN (red) enwrapping a neurone (green). Image from Fawcett et al. (2019.
References
Kwok, J.C.F., Dick, G., Wang, D. and Fawcett, J.W. 2011. Extracellular matrix and perineuronal nets in CNS repair. Developmental Neurobiology. 71(11), pp.1073-1089.
Sorg, B.A., Berretta, S., Blacktop, J.M., Fawcett, J.W., Kitagawa, H., Kwok, J.C. and Miquel, M. 2016. Casting a Wide Net: Role of Perineuronal Nets in Neural Plasticity. J Neurosci. 36(45), pp.11459-11468.