Chondroitin 6-sulphate is required for neuroplasticity and memory in ageing

Abstract

Perineuronal nets (PNNs) are chondroitin sulphate proteoglycan-containing structures on the neuronal surface that have been implicated in the control of neuroplasticity and memory. Age-related reduction of chondroitin 6-sulphates (C6S) leads to PNNs becoming more inhibitory. Here, we investigated whether manipulation of the chondroitin sulphate (CS) composition of the PNNs could restore neuroplasticity and alleviate memory deficits in aged mice. We first confirmed that aged mice (20-months) showed memory and plasticity deficits. They were able to retain or regain their cognitive ability when CSs were digested or PNNs were attenuated. We then explored the role of C6S in memory and neuroplasticity. Transgenic deletion of chondroitin 6-sulfotransferase (chst3) led to a reduction of permissive C6S, simulating aged brains. These animals showed very early memory loss at 11 weeks old. Importantly, restoring C6S levels in aged animals rescued the memory deficits and restored cortical long-term potentiation, suggesting a strategy to improve age-related memory impairment.

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Item Type:	Article
Authors/Creators:	Yang, S Gigout, S https://orcid.org/0000-0002-2966-8843 Molinaro, A Naito-Matsui, Y Hilton, S Foscarin, S Nieuwenhuis, B Tan, CL Verhaagen, J Pizzorusso, T Saksida, LM Bussey, TM Kitagawa, H Kwok, JCF https://orcid.org/0000-0002-9798-9083 Fawcett, JW
Copyright, Publisher and Additional Information:	© The Author(s) 2021. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Dates:	Published: October 2021 Published (online): 16 July 2021 Accepted: 23 June 2021
Institution:	The University of Leeds
Academic Units:	The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Biomedical Sciences (Leeds)
Funding Information:	Funder Grant number MRC (Medical Research Council) MC_PC_16050 MRC (Medical Research Council) MR/S011110/1
Depositing User:	Symplectic Publications
Date Deposited:	24 Jun 2021 15:26
Last Modified:	25 Aug 2022 16:10
Status:	Published
Publisher:	Springer Nature
Identification Number:	10.1038/s41380-021-01208-9
Open Archives Initiative ID (OAI ID):	oai:eprints.whiterose.ac.uk:175539

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Chondroitin 6-sulphate is required for neuroplasticity and memory in ageing

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