The effect of celastrol on learning and memory in diabetic rats after sevoflurane inhalation.

Introduction: The aim was to devise an animal model showing some of the neuropathological changes seen in senile dementia, and to investigate the effect of celastrol on cognition neuropathology in this model.

Material And Methods: Forty male Sprague Dawley rats weighing 300-350 g were randomly divided into 5 groups ( = 8 each): control (Con); inhaled sevoflurane (Sev); diabetes mellitus (DM); diabetes mellitus + inhaled sevoflurane (DM/Sev); diabetes + inhaled sevoflurane + celastrol (Cel). Diabetes was induced by an intraperitoneal injection of streptozotocin (STZ). After 20 days, the Sev, DM/Sev and Cel group rats inhaled 3% sevoflurane for 2 h, while the control and DM groups inhaled air. Cel group rats were given intraperitoneal injections of celastrol (0.7 mg/kg) daily for 4 days, while the control group received intraperitoneal injections of an equal volume of dimethylsulfoxide. The Morris water maze test was performed to test cognition. Animals were killed after the last water maze test and Congo red staining was used to observe deposition of amyloid substance in the hippocampus. The expression of GFAP and IGF-1 in the hippocampus was observed by immunohistochemistry.

Results: Diabetes decreased cognition, increased amyloid substance and GFAP expression, and decreased IGF-1 expression in the hippocampus (all -values < 0.05). Sevoflurane administration intensified and celastrol decreased these changes (all -values < 0.05).

Conclusions: Sev/DM rats showed cognitive and neurochemical changes similar to those seen in senile dementia. Celastrol decreased these changes and should be evaluated further as a possible clinical agent in dementia.