Perineuronal Nets in Spinal Motoneurones: Chondroitin Sulphate Proteoglycan around Alpha Motoneurones.

Sian Irvine,Jessica Kwok

doi:10.3390/ijms19041172

Sian Irvine, Jessica Kwok

Open Access

https://doi.org/10.3390/ijms19041172

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Abstract

Perineuronal nets (PNNs) are extracellular matrix structures surrounding neuronal sub-populations throughout the central nervous system, regulating plasticity. Enzymatically removing PNNs successfully enhances plasticity and thus functional recovery, particularly in spinal cord injury models. While PNNs within various brain regions are well studied, much of the composition and associated populations in the spinal cord is yet unknown. We aim to investigate the populations of PNN neurones involved in this functional motor recovery. Immunohistochemistry for choline acetyltransferase (labelling motoneurones), PNNs using Wisteria floribunda agglutinin (WFA) and chondroitin sulphate proteoglycans (CSPGs), including aggrecan, was performed to characterise the molecular heterogeneity of PNNs in rat spinal motoneurones (Mns). CSPG-positive PNNs surrounded ~70–80% of Mns. Using WFA, only ~60% of the CSPG-positive PNNs co-localised with WFA in the spinal Mns, while ~15–30% of Mns showed CSPG-positive but WFA-negative PNNs. Selective labelling revealed that aggrecan encircled ~90% of alpha Mns. The results indicate that (1) aggrecan labels spinal PNNs better than WFA, and (2) there are differences in PNN composition and their associated neuronal populations between the spinal cord and cortex. Insights into the role of PNNs and their molecular heterogeneity in the spinal motor pools could aid in designing targeted strategies to enhance functional recovery post-injury.

Highlights

Perineuronal nets (PNNs) are dense specialised extracellular matrix (ECM) structures that surround neuronal sub-populations throughout the central nervous system (CNS)
Alongside choline acetyltransferase (ChAT) staining, we stained for Wisteria floribunda agglutinin (WFA), a common PNN marker [6,7,10,34], and for chondroitin sulphate proteoglycans (CSPGs) including aggrecan (ACAN), brevican (BCAN), neurocan (NCAN), versican (VCAN) and phosphacan (PTPRZ)
Despite the clinical relevance of PNNs targeted for CNS repair and regeneration, in locomotor recovery models of spinal cord injury (SCI), the functional relationship between PNNs and the motor system is still mostly unexplored

Summary

Introduction

Perineuronal nets (PNNs) are dense specialised extracellular matrix (ECM) structures that surround neuronal sub-populations throughout the central nervous system (CNS). PNNs are composed of a compact arrangement of a variety of neural ECM proteoglycans and proteins [12,13] These components primarily consist of chondroitin sulphate proteoglycans (CSPGs) including the hyaluronan (HA) binding CSPGs called lecticans, bound upon a long HA backbone and stabilised by the HA and proteoglycan link proteins (HAPLNs) and tenascin-R [14]. Upon this basic PNN structure, the binding of other CSPGs (such as phosphacan) are thought to provide much of the heterogeneity of PNNs [15]. CS-GAGs confer a further vast degree of heterogeneity through variation of expression, chain length and sulphation patterns, even to the same core protein [16,17]

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