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

Neurochem Res. 2020 Aug;45(8):1769-1780. doi: 10.1007/s11064-020-03039-6. Epub 2020 May 15.


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.

Keywords: Cerebellum; Diabetes; Gastrodin; Motor learning.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Behavior, Animal / drug effects*
  • Benzyl Alcohols / therapeutic use*
  • Cerebellar Cortex / drug effects
  • Cerebellar Cortex / enzymology
  • Cerebellar Cortex / pathology
  • Cognitive Dysfunction / drug therapy*
  • Cognitive Dysfunction / epidemiology
  • Diabetes Mellitus, Experimental / complications
  • Endothelium, Vascular / drug effects
  • Glucosides / therapeutic use*
  • Locomotion / drug effects*
  • Male
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase / metabolism
  • Purkinje Cells / drug effects
  • Rats, Sprague-Dawley
  • Signal Transduction / drug effects
  • Vascular Endothelial Growth Factor A / metabolism
  • Vascular Endothelial Growth Factor Receptor-2 / metabolism


  • Benzyl Alcohols
  • Glucosides
  • Vascular Endothelial Growth Factor A
  • Nitric Oxide
  • gastrodin
  • Nitric Oxide Synthase
  • Vascular Endothelial Growth Factor Receptor-2