Regulation of CNS Plasticity Through the Extracellular Matrix

Abstract

Contrary to established dogma, the central nervous system (CNS) has a capacity for regeneration and is moderately plastic. Traditionally, such changes have been recognized through development, but more recently, this has been documented in adults through learning and memory or during the advent of trauma and disease. One of the causes of such plasticity has been related to changes in the extracellular matrix (ECM). This complex scaffold of sugars and proteins in the extracellular space alters functionality of the surrounding tissue through moderation of synaptic connections, neurotransmission, ion diffusion, and modification to the cytoskeleton. This chapter discusses the role of the ECM in CNS plasticity in development and the adult. Further, it determines how the ECM affects normal neuronal functioning in critical processes such as memory. Finally, the chapter assesses how the ECM contributes to adverse CNS changes in injury and disease, concentrating on how this matrix may be targeted for therapeutic intervention.

New insights into glial scar formation after spinal cord injury

“…Embryonic rat dorsal root ganglion neurons are less sensitive to the inhibitory myelin protein, Nogo-A, whereas by post-natal day 6, the same rat neuron growth cones collapse when exposed to the molecule (Bandtlow 2003 ). The decreased presence of axon-inhibitory structures such as the scar or perineuronal nets laden with growth inhibitory CSPGs (which do not form until the end of the critical period) plays a vital role (Celio et al 1998 ; Takesian and Hensch 2013 ; Warren et al 2018a ). Specific CSPGs, such as phosphacan, are more highly expressed in the glial scar of the adult compared to the wound response in the neonate (McKeon et al 1995 ).…”

“…In the spinal cord, the majority of PNNs are found in the ventral motor horn (Irvine and Kwok 2018 ). Circuit stability is conferred by CSPGs (Warren and Alilian 2018 ; Warren et al 2018a ; Carulli and Verhaagen 2021 ). Perhaps through dampening autophagic flux (Tran et al 2020 ), CSPGs through protein tyrosine phosphatase receptor sigma (PTPRσ) binding promote initial adhesion and receptor recruitment necessary for synaptogenesis (Han et al 2016 ; Bomkamp et al 2019 ).…”

Proteoglycans as Therapeutic Targets in Brain Cancer

“…The modification of PGs in ECM is shown as one of the factors leading to change in CNS plasticity. Through control of neurotransmission and synaptic connections, the scaffold of proteins and sugars in the ECM changes the functionality of surrounding tissue ( 36 ).…”

Attenuation of the extracellular matrix increases the number of synapses but suppresses synaptic plasticity through upregulation of SK channels

“…Attenuation of the ECM in the adult brain can potentially restore the brain to an immature state and promote (re-)wiring (Bikbaev et al, 2015). Hence, manipulation of the ECM has been suggested as a way to stimulate brain repair after injury and boost brain plasticity (Burnside and Bradbury, 2014;Chao et al, 2018). Nevertheless, the role of ECM in synaptic plasticity remains controversial (Dityatev and Schachner, 2003;Senkov et al, 2014).…”