机构：[1]Department of Pathology and Pathophysiology, Faculty of Basic Medical Sciences, Kunming Medical University, Kunming, China,[2]Department of Thoracic Surgery, First Affiliated Hospital of Kunming Medical University, Kunming, China,外科科室胸外科昆明医科大学附属第一医院[3]Department of Orthopedics, The Fifth Affiliated Hospital, Kunming Medical University, Kunming, China,外科科室骨科[4]Institute of Drug Discovery and Development, Kunming Pharmaceutical Corporation, Kunming, China,[5]The Key Laboratory of Stem Cell and Regenerative Medicine of Yunnan Province, Kunming Medical University, Kunming, China,[6]Emergency Department, First Affiliated Hospital of Kunming Medical University, Kunming, China,内科科室急诊医学科昆明医科大学附属第一医院[7]The Second Affiliated Hospital of Kunming Medical University, Kunming, China,[8]Department of Morphological Laboratory, Faculty of Basic Medical Sciences, Kunming Medical University, Kunming, China,[9]Biomedical Engineering Research Center, Kunming Medical University, Kunming, China,[10]Institute of Neuroregeneration and Neurorehabilitation, Department of Neurosurgery of the Affiliated Hospital, Qingdao University, Qingdao, China
Cognitive dysfunction is a very severe consequence of diabetes, but the underlying causes are still unclear. Recently, the 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 a 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 pathway-related factors, including GluR2, protein kinase C (PKC), NR2A, and nNOS, in the cerebellar cortex were evaluated by western blotting and double immunofluorescence. The NO concentration was measured. The cellular degeneration and the 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, the 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, and this was coupled with the elevation of the protein expression of the abovementioned biomarkers. Arising from the above, we concluded that gastrodin may contribute to the improvement of motor learning by protecting the LTD pathways in Purkinje cells.
基金：
This study was supported in part by the National Natural
Science Foundation of China (Grant Nos. 81760149, 81460210,
81360176, 31760292, 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), and the Yunnan
Provincial Education Commission (Grant Nos. 2018JS156,
2018Y040, and 2013Z105).
第一作者机构：[2]Department of Thoracic Surgery, First Affiliated Hospital of Kunming Medical University, Kunming, China,
共同第一作者：
通讯作者：
推荐引用方式(GB/T 7714)：
Cheng-Kun Deng,Zhi-Hao Mu,Yi-He Miao,et al.Gastrodin Ameliorates Motor Learning Deficits Through Preserving Cerebellar Long-Term Depression Pathways in Diabetic Rats[J].FRONTIERS IN NEUROSCIENCE.2019,13:doi:10.3389/fnins.2019.01239.
APA：
Cheng-Kun Deng,Zhi-Hao Mu,Yi-He Miao,Yi-Dan Liu,Lei Zhou...&Ying-Ying Zou.(2019).Gastrodin Ameliorates Motor Learning Deficits Through Preserving Cerebellar Long-Term Depression Pathways in Diabetic Rats.FRONTIERS IN NEUROSCIENCE,13,
MLA：
Cheng-Kun Deng,et al."Gastrodin Ameliorates Motor Learning Deficits Through Preserving Cerebellar Long-Term Depression Pathways in Diabetic Rats".FRONTIERS IN NEUROSCIENCE 13.(2019)
