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Early Intervention of Gastrodin Improved Motor Learning in Diabetic Rats Through Ameliorating Vascular Dysfunction

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Abstract

The mechanism of cognitive dysfunction in diabetes is still unclear. Recently, studies have shown that the cerebellum is involved in cognition. Furthermore, diabetes-induced cerebellar alterations is related to vascular changes. Therefore, we aimed to explore the roles of vascular function in diabetes-induced cerebellar damage and motor learning deficits. Type 1 diabetes was induced by a single injection of streptozotocin in Sprague–Dawley rats. Motor learning was assessed by beam walk test and beam balance test. The pathological changes of the cerebellum were assessed by Hematoxylin and eosin staining and Nissl staining. Apoptosis was evaluated by anti-caspase-3 immunostaining. Protein expression was evaluated by western blotting and double immunofluorescence. Our results have shown that motor learning was impaired in diabetic rats, coupled with damaged Purkinje cells and decreased capillary density in the cerebellum. In addition, the protein expression of neuronal NOS, inducible NOS, endothelial NOS, total nitric oxide, vascular endothelial growth factor and its cognate receptor Flk-1 was decreased in the cerebellum. Gastrodin treatment ameliorated neuronal damage and restored protein expression of relevant factors. Arising from the above, it is suggested that vascular dysfunction and NO signaling deficits in the cerebellum may be the underlying mechanism of early manifestations of cognitive impairment in diabetes, which could be ameliorated by gastrodin intervention.

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Data Availability

The raw data supporting the conclusions of this manuscript will be made available by the authors, without undue reservation, to any qualified researcher.

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Funding

The present study was supported in part by the National Natural Science Foundation of China (Grant Nos. 81760149, 81360176 and 81200840), the Department of Science and Technology of Yunnan Province (Grant No. 2013HB078), the Joint Special Funds for the Department of Science and Technology of Yunnan Province-Kunming Medical University [Grant Nos. 2017FE468 (-171) and 2017FE468 (-012)], and the Yunnan Provincial Education Commission (Grant No. 2018JS156).

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Author notes

  1. Fan Zhang, Cheng-Kun Deng, and Yong-Jie Huang have contributed equally to this work.

Authors and Affiliations

  1. Department of Pathology and Pathophysiology, Faculty of Basic Medical Sciences, Kunming Medical University, 1168 West Chunrong Road, Kunming, 650500, China

    Fan Zhang, Cheng-Kun Deng, Yong-Jie Huang, Yi-He Miao, Yao-Yi Wang, Ying Zhang, Wei-Quan Zhang, Rui-Dong Zhou, Bao Lei, Xin Shen, Xing-Yan Wu, Ge Cui, Zhi-Hao Mu & Ying-Ying Zou

  2. The Second Faculty of Clinical Medicine, Kunming Medical University, Kunming, China

    Fan Zhang & Yao-Yi Wang

  3. Department of Thoracic Surgery, First Affiliated Hospital of Kunming Medical University, Kunming, China

    Cheng-Kun Deng

  4. Emergency Department, First Affiliated Hospital of Kunming Medical University, Kunming, China

    Yong-Jie Huang

  5. Orthopedics Department, Fifth Affiliated Hospital, Kunming Medical University, Kunming, China

    Yi-He Miao

  6. The Pediatric of the First Affiliated of Kunming Medical University, Kunming, China

    Ying Zhang & Wei-Quan Zhang

  7. Department of Morphological Laboratory, Faculty of Basic Medical Sciences, Kunming Medical University, Kunming, China

    Zhong-Yi Qian

  8. The First Faculty of Clinical Medicine, Kunming Medical University, Kunming, China

    Bao Lei, Xin Shen & Xing-Yan Wu

  9. Electron Microscope Laboratory, Kunming Medical University, Kunming Medical University, Kunming, China

    Jing-Ling Song

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  1. Fan Zhang
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Contributions

YYZ, ZHM and JLS designed the project and finalized the manuscript. FZ, CKD and YJH performed the majority of the experiments, participated in discussion, analyzed the data, and prepared the first draft of the manuscript. YHM, YYW and YZ conducted the part of experiments, participated in discussion, and analyzed the data. ZYQ, WQZ and RDZ performed the paraffin embedding, sectioning, and H&E staining. BL, XS, XYW and GC conducted part of the experiments and helped with removal of tissue samples and took care of the experimental rats.

Corresponding authors

Correspondence to Jing-Ling Song, Zhi-Hao Mu or Ying-Ying Zou.

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Animal procedures were reviewed and approved by the Medical Ethics Committee of Kunming Medical University, Kunming, China.

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Zhang, F., Deng, CK., Huang, YJ. et al. Early Intervention of Gastrodin Improved Motor Learning in Diabetic Rats Through Ameliorating Vascular Dysfunction. Neurochem Res 45, 1769–1780 (2020). https://doi.org/10.1007/s11064-020-03039-6

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