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Trimethyltin chloride (TMT) is a potent neurotoxin to cause neurodegeneration, especially in hippocampus. This study aimed to identify dietary components that can effectively attenuate TMT-induced neurodegeneration in humans. The predominant anthocyanin in human diets, cyanidin-3-O-glucoside (C3G, 5 or 50 mg/kg), was given to mice for 16 days, and TMT (2.7 mg/kg) was injected intraperitoneally once on the eighth day. C3G (50 mg/kg) significantly alleviated TMT-induced seizures and subsequent cognitive impairment by ameliorating hippocampal neurodegeneration and synaptic dysfunction. Furthermore, C3G treatment restored glutamate homeostasis in brain and reversed glutamine synthetase (GS) inhibition in reactive astrogliosis and neuroinflammation, which are critical for C3G’s neuroprotective effects. Notably, C3G decreased the lipopolysaccharide, tumor necrosis factor-α, interleukin-6, and interleukin-1β levels in the mice, which potentially by modulating the relative abundance of Atopobiaceae and Lachnospiraceae in the gut. C3G may be a promising and practical dietary component for reducing TMT-induced neurodegeneration.


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Cyanidin-3-O-glucoside alleviates trimethyltin chloride-induced neurodegeneration by maintaining glutamate homeostasis through modulation of the gut microbiota

Show Author's information Yu Xi,Wenhui LiJunru WangMeihong YuXiangquan ZengHe Li( )Jian Li( )
Key Laboratory of Green and Low-Carbon Processing Technology for Plant-Based Food of China National Light Industry Council, Beijing Advanced Innovation Center for Food Nutrition and Human Health, Beijing Technology and Business University, Beijing 100048, China

Peer review under responsibility of Tsinghua University Press.

Highlights

1. C3G ameliorates TMT-induced hippocampal neurodegeneration and synaptic dysfunction.

2. Glutamate brain homeostasis disruption in neurodegeneration is restored by C3G.

3. Glutamine synthetase was critical to the C3G neuroprotective effects.

4. Modulation of gut microbiota protects astrocytes and glutamate brain homeostasis.

Abstract

Trimethyltin chloride (TMT) is a potent neurotoxin to cause neurodegeneration, especially in hippocampus. This study aimed to identify dietary components that can effectively attenuate TMT-induced neurodegeneration in humans. The predominant anthocyanin in human diets, cyanidin-3-O-glucoside (C3G, 5 or 50 mg/kg), was given to mice for 16 days, and TMT (2.7 mg/kg) was injected intraperitoneally once on the eighth day. C3G (50 mg/kg) significantly alleviated TMT-induced seizures and subsequent cognitive impairment by ameliorating hippocampal neurodegeneration and synaptic dysfunction. Furthermore, C3G treatment restored glutamate homeostasis in brain and reversed glutamine synthetase (GS) inhibition in reactive astrogliosis and neuroinflammation, which are critical for C3G’s neuroprotective effects. Notably, C3G decreased the lipopolysaccharide, tumor necrosis factor-α, interleukin-6, and interleukin-1β levels in the mice, which potentially by modulating the relative abundance of Atopobiaceae and Lachnospiraceae in the gut. C3G may be a promising and practical dietary component for reducing TMT-induced neurodegeneration.

Keywords: Gut microbiota, Neurodegeneration, Cyanidin-3-O-glucoside, Trimethyltin, Glutamatergic pathway

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Publication history

Received: 17 January 2023
Revised: 16 February 2023
Accepted: 06 March 2023
Published: 25 September 2023
Issue date: March 2024

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© 2024 Beijing Academy of Food Sciences. Publishing services by Tsinghua University Press.

Acknowledgements

Acknowledgements

This work was supported by the National Natural Science Foundation of China (81903275) and the fund of Cultivation Project of Double First-Class Disciplines of Food Science and Engineering, Beijing Technology & Business University (BTBUYXTD202203).

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This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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