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Safflower Yellow Improves Synaptic Plasticity in APP/PS1 Mice by Regulating Microglia Activation Phenotypes and BDNF/TrkB/ERK Signaling Pathway

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Abstract

Alzheimer’s disease (AD) is a common neurodegenerative disease that is always accompanied by synaptic loss in the brain. Safflower yellow (SY) is the extract of safflower, a traditional Chinese medicine, which has shown neuroprotective effects in recent studies. However, the mechanism of SY in protecting synapses remains unclear. In this study, we are going to study the mechanism of how SY treats AD in terms of synaptic plasticity. We found, via behavioral experiments, that SY treatment could improve the abilities of learning and memory in APP/PS1 mice. In addition, using Golgi staining and HE staining, we found that SY treatment could reduce the loss of dendritic spines in the pathological condition and could maintain the normal physiological state of the cells in cortex and in hippocampus. In addition, the results of immunofluorescence staining and western blotting showed that SY treatment could significantly increase the expression of synapse-related proteins. Moreover, after being treated with SY, the expression of iNOS (marker of M1 microglia) declined remarkably, and the level of Arginase-1 (marker of M2 microglia) increased significantly. Finally, we found BDNF/TrkB/ERK signaling cascade was activated. These results indicate that SY enhances synaptic plasticity in APP/PS1 mice by regulating microglia activation phenotypes and BDNF/TrkB/ERK signaling pathway.

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Acknowledgements

Thanks to American Journal Experts for providing language help in this article (Certificate Verification Key: 2840-1165-087E-4316-0A08).

Funding

This research was supported by the National Natural Science Foundation of China [Nos. 81660603 and 81960665].

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  1. Jie Pang and Jiawei Hou contributed equally to this work.

Authors and Affiliations

  1. Key Laboratory of Xinjiang Phytomedicine Resource and Utilization, Ministry of Education, Department of Pharmacology, Shihezi University, Shihezi, 832000, Xinjiang, People’s Republic of China

    Jie Pang, Jiawei Hou, Zhangjiuzhi Zhou, Mengqiao Ren, Yuyan Mo, Guang Yang, Zuwei Qu & Yanli Hu

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  1. Jie Pang
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  2. Jiawei Hou
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Contributions

JP and YH conceived and designed research. JP and JH conducted experiments. ZZ, MR, YM and JH analyzed data. JH wrote the manuscript; GY, ZQ and YH revised the manuscript. All authors read and approved the manuscript for publication.

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Correspondence to Yanli Hu.

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Pang, J., Hou, J., Zhou, Z. et al. Safflower Yellow Improves Synaptic Plasticity in APP/PS1 Mice by Regulating Microglia Activation Phenotypes and BDNF/TrkB/ERK Signaling Pathway. Neuromol Med 22, 341–358 (2020). https://doi.org/10.1007/s12017-020-08591-6

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