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.

中文翻译：

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天麻素的早期干预通过改善血管功能障碍改善了糖尿病大鼠的运动学习。

糖尿病的认知功能障碍的机制仍不清楚。最近，研究表明小脑与认知有关。此外，糖尿病引起的小脑改变与血管变化有关。因此，我们旨在探讨血管功能在糖尿病引起的小脑损伤和运动学习障碍中的作用。在Sprague-Dawley大鼠中单次注射链脲佐菌素可诱发1型糖尿病。运动学习通过束步测试和束平衡测试进行评估。通过苏木精和曙红染色和尼氏染色评估小脑的病理变化。通过抗caspase-3免疫染色评估细胞凋亡。通过蛋白质印迹和双重免疫荧光评估蛋白质表达。我们的结果表明，糖尿病大鼠的运动学习受到损害，加上受损的浦肯野细胞和小脑毛细血管密度降低。另外，小脑中神经元NOS，诱导型NOS，内皮NOS，一氧化氮，血管内皮生长因子及其相关受体Flk-1的蛋白表达降低。天麻素治疗可改善神经元损伤并恢复相关因子的蛋白表达。综上所述，提示小脑血管功能障碍和NO信号缺乏可能是糖尿病认知障碍早期表现的潜在机制，天麻素干预可改善这种机制。小脑血管内皮生长因子及其相关受体Flk-1减少。天麻素治疗可减轻神经元损伤并恢复相关因子的蛋白表达。综上所述，提示小脑血管功能障碍和NO信号缺乏可能是糖尿病认知障碍早期表现的潜在机制，天麻素干预可改善这种机制。小脑血管内皮生长因子及其相关受体Flk-1减少。天麻素治疗可改善神经元损伤并恢复相关因子的蛋白表达。综上所述，提示小脑血管功能障碍和NO信号缺乏可能是糖尿病认知障碍早期表现的潜在机制，天麻素干预可改善这种机制。