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The neuroprotective effects of peracetylated chitosan oligosaccharides against β-amyloid-induced cognitive deficits in rats

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Abstract

Chitosan oligosaccharides (COSs) have been reported to possess a broad range of activities such as antitumor, antioxidant and neuroprotective activities. In this study, the protective effects and mechanisms of peracetylated chitosan oligosaccharides (PACOs) against Aβ-induced cognitive deficits were investigated in Sprague–Dawley (SD) rats. PACOs treatment significantly improved the learning and memory function of Alzheimer’s disease (AD) rats and attenuated the neuron cell damage caused by Aβ. PACOs also markedly reduced the levels of lactate dehydrogenase (LDH) and Malondialdehyde (MDA) and decreased the phosphorylation of Tau protein to inhibit oxidative injury and inflammatory responses in AD rats. Further studies indicated that PACOs may promote the repair of Aβ induced nerve damage and inhibit neuronal apoptosis mainly through regulating PI3K/Akt/GSK3β signaling pathway. Consistently, the transcriptome analysis verified that the differentially expressed genes (DEGs) were mainly involved in neuron development and the PI3K-Akt signaling pathway. Taken together, peracetylated chitosan oligosaccharides (PACOs) have the potential to be developed into novel anti-AD agents targeting the cellular PI3K/Akt/GSK3β signaling pathway.

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Data availability

The data that supports the findings of this study are included in this published article (and its supplementary information file).

Abbreviations

Aβ:

β-Amyloid

AD:

Alzheimer’s disease

COSs:

Chitosan oligosaccharides

DEGs:

Differentially expressed genes

GSK3β:

Glycogen synthase kinase 3β

HE:

Hematoxylin–eosin

MDA:

Malondialdehyde

MWM:

Morris water maze

PACOs:

Peracetylated chitosan oligosaccharides

PI3K:

Phosphoinositide 3-kinase

SOD:

Superoxide dismutase

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Acknowledgements

This work was supported by National Natural Science Foundation of China (31500646, 81874320, and 81672585), Shandong Major Science and Technology Project (2021ZDSYS22), the Promotive Research Fund for Excellent Young and Middle-aged Scientists of Shandong Province (BS2015YY040), Qingdao Science and Technology Development project (15-9-1-67-JCH) and Youth Research Fund of Affiliated Hospital of Qingdao University (QDFYQN202101003).

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Author notes

  1. Cui Hao and Minmin Han have contributed equally to this work.

Authors and Affiliations

  1. Medical Research Center, Affiliated Hospital of Qingdao University, Qingdao, 266003, China

    Cui Hao, Minmin Han, Yunliang Guo & Lijuan Zhang

  2. Key Laboratory of Marine Drugs, Ministry of Education, Ocean University of China, Qingdao, 266003, China

    Cui Hao, Wei Wang, Cheng Yang & Chunxia Li

  3. Center of Integrated Traditional and Western Medicine, Qingdao University, Qingdao, 266003, China

    Cui Hao, Minmin Han, Yunliang Guo & Tao Xu

  4. Qingdao Women’s and Children’s Hospital, Qingdao, 266003, China

    Minmin Han & Tao Xu

  5. Department of Pathology, Affiliated Hospital of Qingdao University, Qingdao, 266003, China

    Jigang Wang

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  1. Cui Hao
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  2. Minmin Han
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  3. Wei Wang
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Contributions

Conceptualization: CH, CXL and TX; Formal Analysis and Investigation: MMH, CY, QHZ; Validation and Visualization: MMH, CH, WW; Project Administration and Funding Acquisition: CH, WW, CXL; Writing-original draft: CH, WW; Writing-review and editing: WW, CXL, YLG, LJZ. All authors have read and agreed to the published version of the manuscript.

Corresponding authors

Correspondence to Cui Hao or Chunxia Li.

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The authors declare no conflict of interest.

Animal and human rights statement

This article does not contain any studies with human participants performed by any of the authors. All animal experimental protocols in this study were approved by the Research Review Committee of the affiliated hospital of Qingdao University (No. 201612A001). All animal experiments were carried out in accordance with internationally valid guidelines of the Standards for Laboratory Animals of China (GB 14922.2-2001, GB 14923-2001, and GB 14925-2001).

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Edited by Chengchao Chen.

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Hao, C., Han, M., Wang, W. et al. The neuroprotective effects of peracetylated chitosan oligosaccharides against β-amyloid-induced cognitive deficits in rats. Mar Life Sci Technol 5, 211–222 (2023). https://doi.org/10.1007/s42995-023-00172-3

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