Gastrodin Ameliorates Motor Learning Deficits Through Preserving Cerebellar Long-Term Depression Pathways in Diabetic Rats

Cheng-Kun Deng; Zhi-Hao Mu; Yi-He Miao; Yi-Dan Liu; Lei Zhou; Yong-Jie Huang; Fan Zhang; Yao-Yi Wang; Zhi-Hong Yang; Zhong-Yi Qian; Xie Wang; Jia-Zhi Guo; Mei-Yan Zhang; Xin-Yu Liao; Qi Wan; Di Lu; Ying-Ying Zou

doi:10.3389/fnins.2019.01239

Gastrodin Ameliorates Motor Learning Deficits Through Preserving Cerebellar Long-Term Depression Pathways in Diabetic Rats

Front Neurosci. 2019 Nov 22:13:1239. doi: 10.3389/fnins.2019.01239. eCollection 2019.

Authors

Cheng-Kun Deng^{1

2}, Zhi-Hao Mu¹, Yi-He Miao^{1

3}, Yi-Dan Liu⁴, Lei Zhou⁵, Yong-Jie Huang^{1

6}, Fan Zhang^{1

7}, Yao-Yi Wang^{1

7}, Zhi-Hong Yang¹, Zhong-Yi Qian⁸, Xie Wang¹, Jia-Zhi Guo⁹, Mei-Yan Zhang¹, Xin-Yu Liao¹, Qi Wan¹⁰, Di Lu⁹, Ying-Ying Zou¹

Affiliations

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.
³ Department of Orthopedics, The Fifth Affiliated Hospital, Kunming Medical University, Kunming, China.
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.
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.

Abstract

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.

Keywords: LTD; Purkinje cells; cerebellum; diabetes; gastrodin.