Perineuronal Nets and Their Role in Synaptic Homeostasis

Mateusz Bosiacki 1, Magdalena Ga˛ssowska-Dobrowolska 2, Klaudyna Kojder 3,
Marta Fabianska 4, Dariusz Jezewski 5, Izabela Gutowska 6 and Anna Lubkowska 1,
1 Department of Functional Diagnostics and Physical Medicine, Pomeranian Medical University in Szczecin,Zołnierska 54 Str., 71-210 Szczecin, Poland
2 Department of Cellular Signalling, Mossakowski Medical Research Centre, Polish Academy of Sciences,Pawinskiego 5 Str., 02-106Warsaw, Poland
3 Department of Anaesthesiology and Intensive Care, Pomeranian Medical University in Szczecin,71-252 Szczecin, Poland
4 Institute of Philosophy, University of Szczecin, Krakowska 71-79 Str., 71-017 Szczecin, Poland
5 Department of Neurosurgery and Pediatric Neurosurgery, Department of Applied Neurocognitivistics, Pomeranian Medical University in Szczecin, 71-252 Szczecin, Poland
6 Department of Human Nutrition and Metabolomics, Department of Medical Chemistry, Pomeranian Medical University in Szczecin, Broniewskiego 24 Str., 71-252 Szczecin, Poland

Received: 7 July 2019; Accepted: 16 August 2019; Published: 22 August 2019

Abstract: Extracellular matrix (ECM) molecules that are released by neurons and glial cells form perineuronal nets (PNNs) and modulate many neuronal and glial functions. PNNs, whose structure is still not known in detail, surround cell bodies and dendrites, which leaves free space for synapses to come into contact. A reduction in the expression of many neuronal ECM components adversely a ects processes that are associated with synaptic plasticity, learning, and memory. At the same time, increasedECMactivity, e.g., as a result of astrogliosis following brain damage or in neuroinflammation, can also have harmful consequences. The therapeutic use of enzymes to attenuate elevated neuronal ECM expression after injury or in Alzheimer’s disease has proven to be beneficial by promoting axon growth and increasing synaptic plasticity. Yet, severe impairment of ECM function can also lead to neurodegeneration. Thus, it appears that to ensure healthy neuronal function a delicate balance of ECM components must be maintained. In this paper we review the structure of PNNs and their components, such as hyaluronan, proteoglycans, core proteins, chondroitin sulphate proteoglycans, tenascins, and Hapln proteins. We also characterize the role of ECM in the functioning of the blood-brain barrier, neuronal communication, as well as the participation of PNNs in synaptic plasticity and some clinical aspects of perineuronal net impairment. Furthermore, we discuss the participation of PNNs in brain signaling. Understanding the molecular foundations of the ways that PNNs participate in brain signaling and synaptic plasticity, as well as how they change in
physiological and pathological conditions, may help in the development of new therapies for many degenerative and inflammatory diseases of the brain.

Keywords:perineuronalnets (PNNs); extracellularmatrix(ECM); synaptogenesis; neuronal communication

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