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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Neurosci. | doi: 10.3389/fnins.2019.01239

Gastrodin ameliorates motor learning deficits through preserving cerebellar long-term depression pathways in diabetic rats

Cheng-Kun Deng1, 2,  Zhihao Mu1, Yi-He Miao1, 3, Yi-Dan Liu4, Lei Zhou5, Yong-Jie Huang1, 2, Fan Zhang1, 3, Yao-Yi Wang1, 3, Zhi-Hong Yang1, Zhong-Yi Qian1,  Xie Wang1, Jia-Zhi Guo6, Mei-Yan Zhang1, Xin-Yu Liao1,  Qi Wan7, Di Lu6* and Ying-Ying Zou1*
  • 1School of Basic Medicine, Kunming Medical University, China
  • 2First Affiliated Hospital of Kunming Medical University, China
  • 3The Second Affiliated Hospital of Kunming Medical University, China
  • 4Kunming Pharmaceutical Group Co., Ltd., China
  • 5Key Laboratory of Stem Cell and Regenerative Medicine, Kunming Medical University, China
  • 6Biomedical Engineering Research Center, Kunming Medical University, China
  • 7Department of Neurosurgery, Affiliated Hospital of Qingdao University, China

Cognitive dysfunction is a very severe consequence of diabetes, but the underlying causes are still unclear. Recently, cerebellum was reported to play an important role in learning and memory. Since long-term depression (LTD) is a primary cellular mechanism for cerebellar motor learning, we aimed to explore the role of cerebellar LTD pathways in diabetic rats and the therapeutic effect of gastrodin. Diabetes was induced by a single injection of streptozotocin into adult Sprague-Dawley rats. Motor learning ability was assessed by beam walk test. Pathological changes of the cerebellum were assessed by Hematoxylin-Eosin (HE) and Nissl staining. Cellular apoptosis was assessed by anti-caspase-3 immunostaining. Protein expression levels of LTD pathways related factors, including GluR2, PKC, NR2A and nNOS, in the cerebellar cortex were evaluated by western blotting and double immunofluorescence. NO concentration was measured. Cellular degeneration and apoptosis of Purkinje cells were evident in the cerebellum of diabetic rats. Protein expression levels of GluR2 (NC9W: 1.26 ± 0.12; DM9W+S: 0.81±0.07), PKC (NC9W: 1.66 ± 0.10; DM9W+S: 0.58±0.19), NR2A (NC9W: 1.40 ± 0.05; DM9W+S: 0.63±0.06), nNOS (NC9W: 1.26 ± 0.12; DM9W+S: 0.68±0.04) and NO (NC9W: 135.61 ± 31.91; DM9W+S: 64.06±24.01) in the cerebellum were significantly decreased in diabetic rats. Following gastrodin intervention, outcome of motor learning ability was significantly improved (NC9W: 6.70 ± 3.31; DM9W+S: 20.47±9.43; DM9W+G: 16.04±7.10). In addition, degeneration and apoptosis were ameliorated, coupled with elevation of the protein expression of the above-mentioned biomarkers. Arising from the above, we concluded that gastrodin may contribute to the improvement of motor learning through protecting the LTD pathways in Purkinje cells.

Keywords: diabetes, Cerebellum, Purkinje cells (PCs), LTD (Long Term Depression), Gastrodin (GAS)

Received: 17 Mar 2019; Accepted: 01 Nov 2019.

Copyright: © 2019 Deng, Mu, Miao, Liu, Zhou, Huang, Zhang, Wang, Yang, Qian, Wang, Guo, Zhang, Liao, Wan, Lu and Zou. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Prof. Di Lu, Biomedical Engineering Research Center, Kunming Medical University, Kunming, Yunnan Province, China, ludi@kmmu.edu.cn
Prof. Ying-Ying Zou, School of Basic Medicine, Kunming Medical University, Kunming, 650500, Yunnan Province, China, zouyingying@kmmu.edu.cn