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

Sujeong Yang; Sylvain Gigout; Angelo Molinaro; Yuko Naito-Matsui; Sam Hilton; Simona Foscarin; Bart Nieuwenhuis; Chin Lik Tan; Joost Verhaagen; Tommaso Pizzorusso; Lisa M. Saksida; Timothy M. Bussey; Hiroshi Kitagawa; Jessica C.F. Kwok; James W. Fawcett

doi:10.1038/s41380-021-01208-9

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

Sujeong Yang, Sylvain Gigout, Angelo Molinaro, Yuko Naito-Matsui, Sam Hilton, Simona Foscarin, Bart Nieuwenhuis, Chin Lik Tan, Joost Verhaagen, Tommaso Pizzorusso, Lisa M. Saksida, Timothy M. Bussey, Hiroshi Kitagawa, Jessica C.F. Kwok, James W. Fawcett

Molecular Cell Biology

Research output: Contribution to journal › Article › peer-review

35 Citations (Scopus)

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.

Original language	English
Pages (from-to)	5658-5668
Number of pages	11
Journal	Molecular Psychiatry
Volume	26
Issue number	10
DOIs	https://doi.org/10.1038/s41380-021-01208-9
Publication status	Published - 10-2021

All Science Journal Classification (ASJC) codes

Molecular Biology
Cellular and Molecular Neuroscience
Psychiatry and Mental health

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/s41380-021-01208-9

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Yang, S., Gigout, S., Molinaro, A., Naito-Matsui, Y., Hilton, S., Foscarin, S., Nieuwenhuis, B., Tan, C. L., Verhaagen, J., Pizzorusso, T., Saksida, L. M., Bussey, T. M., Kitagawa, H., Kwok, J. C. F., & Fawcett, J. W. (2021). Chondroitin 6-sulphate is required for neuroplasticity and memory in ageing. Molecular Psychiatry, 26(10), 5658-5668. https://doi.org/10.1038/s41380-021-01208-9

@article{a865820971ff4a12b68be72431e2ef10,

title = "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.",

author = "Sujeong Yang and Sylvain Gigout and Angelo Molinaro and Yuko Naito-Matsui and Sam Hilton and Simona Foscarin and Bart Nieuwenhuis and Tan, {Chin Lik} and Joost Verhaagen and Tommaso Pizzorusso and Saksida, {Lisa M.} and Bussey, {Timothy M.} and Hiroshi Kitagawa and Kwok, {Jessica C.F.} and Fawcett, {James W.}",

note = "Publisher Copyright: {\textcopyright} 2021, The Author(s).",

year = "2021",

month = oct,

doi = "10.1038/s41380-021-01208-9",

language = "English",

volume = "26",

pages = "5658--5668",

journal = "Molecular Psychiatry",

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Yang, S, Gigout, S, 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 & Fawcett, JW 2021, 'Chondroitin 6-sulphate is required for neuroplasticity and memory in ageing', Molecular Psychiatry, vol. 26, no. 10, pp. 5658-5668. https://doi.org/10.1038/s41380-021-01208-9

TY - JOUR

T1 - Chondroitin 6-sulphate is required for neuroplasticity and memory in ageing

AU - Yang, Sujeong

AU - Gigout, Sylvain

AU - Molinaro, Angelo

AU - Naito-Matsui, Yuko

AU - Hilton, Sam

AU - Foscarin, Simona

AU - Nieuwenhuis, Bart

AU - Tan, Chin Lik

AU - Verhaagen, Joost

AU - Pizzorusso, Tommaso

AU - Saksida, Lisa M.

AU - Bussey, Timothy M.

AU - Kitagawa, Hiroshi

AU - Kwok, Jessica C.F.

AU - Fawcett, James W.

PY - 2021/10

Y1 - 2021/10

N2 - 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.

AB - 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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JO - Molecular Psychiatry

JF - Molecular Psychiatry

IS - 10

ER -

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

Abstract

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