Introduction: Diabetes mellitus causes adverse changes in the neurological morphology of the hippocampus and prefrontal cortex of the brain by increasing oxidative stress. Trigonelline has antihyperglycemic effects and can inhibit oxidative stress. The aim of this study was to evaluate the protective effect of trigonelline on dendritic changes in hippocampal and prefrontal cortex neurons in diabetic rats. 

Methods: In this experimental study, 32 male Wistar rats in the weight range of 195-235 grams were randomly divided into 4 groups consisting of control, trigonelline-treated control, diabetic and trigonelline-treated diabetic. Oral trigonelline treatment at a dose of 50 mg/kg/day during 7 weeks was done. Diabetes induction was done by single dose injection of intraperitoneal streptozotocin at a dose of 60 mg/kg. Serum glucose and body weight were measured at the beginning and at weeks 4 and 8 after diabetes induction. For evaluation of hippocampal and prefrontal cortex neuronal dendrites, Golgi impregnation method was used. For statistical analysis, one-way ANOVA and Tukey post-tests in SPSS version 16 were used. P<0.05 was considered as a significant level.

Results: Serum glucose level in the diabetic group treated with trigonelline significantly has been reduced compared with the diabetic group (p<0.01). The density of dendritic spines of prefrontal cortex and hippocampal neurons in the diabetic group significantly reduced compared to the control group (p<0.01). Moreover, in the diabetic group treated with trigonelline, dendritic spine density significantly increased compared to the diabetic group (p<0.05).

Conclusion: Trigonelline is hypoglycemic and can prevent reduction of dendritic spines in the prefrontal cortex and the hippocampus of streptozotocin diabetic rats.