Chondroitin 6-sulphate is required for neuroplasticity and memory in ageing.
Authors
Yang, Sujeong
Gigout, Sylvain
Naito-Matsui, Yuko
Hilton, Sam
Foscarin, Simona
Tan, Chin Lik
Verhaagen, Joost
Pizzorusso, Tommaso
Saksida, Lisa M
Bussey, Timothy M
Kitagawa, Hiroshi
Publication Date
2021-10Journal Title
Mol Psychiatry
ISSN
1359-4184
Publisher
Springer Science and Business Media LLC
Volume
26
Issue
10
Pages
5658-5668
Language
en
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
Yang, S., Gigout, S., Molinaro, A., Naito-Matsui, Y., Hilton, S., Foscarin, S., Nieuwenhuis, B., et al. (2021). Chondroitin 6-sulphate is required for neuroplasticity and memory in ageing.. Mol Psychiatry, 26 (10), 5658-5668. https://doi.org/10.1038/s41380-021-01208-9
Description
Funder: Alzheimers research UK
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.
Keywords
Article, /631/378, /631/45, /82/51, /42/44, /42/109, article
Sponsorship
Alzherimers research UK
European research council
Funder references
European Research Council (294502)
Alzheimer's Research UK (ARUK-RF2016A-1)
MRC (G1000864)
Medical Research Council (MR/R004463/1)
MRC (MRC--)
Identifiers
s41380-021-01208-9, 1208
External DOI: https://doi.org/10.1038/s41380-021-01208-9
This record's URL: https://www.repository.cam.ac.uk/handle/1810/333056
Rights
Licence:
http://creativecommons.org/licenses/by/4.0/
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