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

Authors :
Yang, Sujeong
Gigout, Sylvain
Molinaro, Angelo
Naito-Matsui, Yuko
Hilton, Sam
Foscarin, Simona
Nieuwenhuis, Bart
Tan, Chin Lik
Verhaagen, Joost
Pizzorusso, Tommaso
Saksida, Lisa M.
Bussey, Timothy M.
Kitagawa, Hiroshi
Kwok, Jessica C. F.
Fawcett, James W.
Source :
Molecular Psychiatry; October 2021, Vol. 26 Issue: 10 p5658-5668, 11p
Publication Year :
2021

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.

Details

Language :
English
ISSN :
13594184 and 14765578
Volume :
26
Issue :
10
Database :
Supplemental Index
Journal :
Molecular Psychiatry
Publication Type :
Periodical
Accession number :
ejs57140637
Full Text :
https://doi.org/10.1038/s41380-021-01208-9