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C-phycocyanin Mitigates Cognitive Impairment in Doxorubicin-Induced Chemobrain: Impact on Neuroinflammation, Oxidative Stress, and Brain Mitochondrial and Synaptic Alterations

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Abstract

Chemotherapy-induced cognitive impairment (CICI) is a common detrimental effect of cancer treatment, occurring in up to 75% of cancer patients. The widely utilized chemotherapeutic agent doxorubicin (DOX) has been implicated in cognitive decline, mostly via cytokine-induced neuroinflammatory and oxidative and mitochondrial damage to brain tissues. C-phycocyanin (CP) has previously been shown to have potent anti-inflammatory, antioxidant, and mitochondrial protective properties. Therefore, this present study was aimed to investigate the neuroprotective effects of CP against DOX-elicited cognitive impairment and explore the underlying mechanisms. CP treatment (50 mg/kg) significantly improved behavioral deficits in DOX-treated mice. Furthermore, CP suppressed DOX-induced neuroinflammation and oxidative stress, mitigated mitochondrial abnormalities, rescued dendritic spine loss, and increased synaptic density in the hippocampus of DOX-treated mice. Our results suggested that CP improves established DOX-induced cognitive deficits, which could be explained at least partly by inhibition of neuroinflammatory and oxidant stress and attenuation of mitochondrial and synaptic dysfunction.

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Abbreviations

CICI:

Chemotherapy-induced cognitive impairment

CP:

C-phycocyanin

DOX:

Doxorubicin

mPTP:

Mitochondrial permeability transition pore

GSH:

Glutathione

MM:

Mitochondrial membrane potential

MDA:

Malondialdehyde

MWM:

Morris water maze

PSD95:

Postsynaptic density protein 95

ROS:

Reactive oxygen species

SOD:

Superoxide dismutase

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Acknowledgements

The present work was supported by National Natural Science Foundation of China (U1804174), Science and Technology Innovation Talents in the Universities of Henan Province (20HASTIT044), Henan Provincial Key Research and Development and Promotion Project (192102310081).

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Authors and Affiliations

  1. School of Basic Medical Sciences, Henan University of Science and Technology, Luoyang, 471023, China

    Chenying Wang, Lewei Wang, Shunji Pan & Dongmei Wang

  2. Department of Clinical Laboratory Science, First Affiliated Hospital of Henan University of Science and Technology, Luoyang, China

    Chenying Wang

  3. Hangzhou Medical College, Hangzhou, China

    Yuhang Zhao

  4. College of Animal Science and Technology, Henan University of Science and Technology, Luoyang, China

    Yumei Liu

  5. Henan Centre for Engineering and Technology Research On Prevention and Treatment of Liver Diseases, Luoyang, China

    Sanqiang Li

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  1. Chenying Wang
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Wang, C., Zhao, Y., Wang, L. et al. C-phycocyanin Mitigates Cognitive Impairment in Doxorubicin-Induced Chemobrain: Impact on Neuroinflammation, Oxidative Stress, and Brain Mitochondrial and Synaptic Alterations. Neurochem Res 46, 149–158 (2021). https://doi.org/10.1007/s11064-020-03164-2

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