Perineuronal Nets and Their Role in Synaptic Homeostasis

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 affects processes that are associated with synaptic plasticity, learning, and memory. At the same time, increased ECM activity, 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.

Cell-to-Cell Communication in Learning and Memory: From Neuro- and Glio-Transmission to Information Exchange Mediated by Extracellular Vesicles

“…It is worth remembering that the brain cell activity as well as its effects are influenced by the surrounding environment, which includes a variety of cells, but also the molecules of the ECM, produced by the cells themselves. The complex of these components form the perineural net (PNN) [141]. A reduction in the expression of ECM components can affect synaptic plasticity, but an increase in ECM activity (for example, as a result of pathologic astrogliosis) can also be harmful [141].…”

The Density of Perineuronal Nets Increases With Age in the Inferior Colliculus in the Fischer Brown Norway Rat

“…PNs can regulate and promote functional synaptic plasticity (Bukalo et al, 2001;Balmer et al, 2009;de Vivo et al, 2013;Blosa et al, 2015;Bosiacki et al, 2019). Interestingly, a recent study has shown that PN expression in the medial subdivisions of the auditory thalamus may be responsible for precise neural firing in the aging brain (Quraishe et al, 2019).…”

“…PNs can surround a variety of types of neurons throughout the brain although most reports focus on their relationship to GABAergic cells (Kosaka and Heizmann, 1989;Härtig et al, 1992;Sonntag et al, 2015). PNs and their primary molecular component, chondroitin sulfate proteoglycans (CSPGs), are critical for numerous functions including ion buffering, stabilizing high-rate synaptic transmission, modulating cellular integrity, neuroprotection, mechanical stabilization of synaptic contacts, and inhibition of structural plasticity (see reviews Sonntag et al, 2015;Bosiacki et al, 2019;Testa et al, 2019). Of these functions the inhibition of plasticity has garnered the most attention as the enzymatic disruption of PNs can restore juvenile-like plasticity in the adult cortex (Pizzorusso et al, 2002(Pizzorusso et al, , 2006Gogolla et al, 2009).…”

“…Of these functions the inhibition of plasticity has garnered the most attention as the enzymatic disruption of PNs can restore juvenile-like plasticity in the adult cortex (Pizzorusso et al, 2002(Pizzorusso et al, , 2006Gogolla et al, 2009). This apparent role for PNs in the diminished neural plasticity that characterizes the aging brain, along with an increasing aging population, has generated strong interest in the role of PNs in the cortex during neurodegenerative diseases and aging (see reviews Burke and Barnes, 2006;Karetko and Skangiel-Kramska, 2009;Bosiacki et al, 2019;Duncan et al, 2019;Testa et al, 2019).…”

Disrupted structural connectivity in ArcAβ mouse model of Aβ amyloidosis

“…The most well-studied type of ECM is Perineuronal Nets (PNN). This lattice-like structure envelop the soma, stabilizing interneuron activity, regulating synaptic homeostasis (Bosiacki et al, 2019) and protecting interneurons from oxidative damage (Morawski et al, 2004). The role of PNN in mouse model of Aβ amyloidosis have been inconsistent and contradictory.…”