Rosiglitazone prevents gliosis,oxidative/nitrative stress and memory deficits induced by intracerebroventricular injection of streptozotocin in rats

Objective To study the preventive effect of rosiglitazone glial activation,oxidative/nitrative stress and spatial memory deficits induced by intracerebroventricular(ICV)injection of streptozotocin(STZ)in rats.Methods 24 male Wistar rats were randomly divided into sham operated group,model group and rosiglitazone group.The model of Alzheimer's was induced by injection with ICV 10% STZ bilaterally,on day 1 and 3(3 mg·kg-1).The rats were treated with rosiglitazone(2 mg·kg-1,p.o.)for a consecutive 21 days,once a day,beginning 7 days prior to STZ injection.The learning and memory behavior was assessed using Morris water maze task and Y-maze 21 d after ICV STZ injection.Malondialdehyde(MDA),superoxide dismutase(SOD),glutathione(GSH)levels and nitrotyrosine immunoreactivity in brain were estimated as parameters of oxidative/nitrative stress.Brain acetyl cholinesterase(AchE)activity was measured by EllMann's method and activated microglia and astrocytes were detected by immunohistochemistry.Results ICV STZ injection resulted in a severe deficit in spatial learning and memory associated with increased MDA level(+69.5%)and nitrotyrosine immunoreactivity(+23.7%),decreased SOD activity(-29.2%)and GSH(-25.1%)in brain.It also showed the activated microglia and astrocytes in the cortex and hippocampal CA1 region and a significant decrease in acetylcholinesterase activity(-40.2%).Compared with model group,chronic administration of rosiglitazone significantly shorten the escape latency time from the third day in place navigation test,increase the number of passing through primary flat place in spatial probe test in Morris water maze test,and decrease the error times in Y-maze test(P<0.05 or P<0.01).In addition,it also prevented the glial changes,decreased the elevated MDA and nitrite levels and restored the depleted GSH and acetylcholinesterase activity in cortex(P<0.05),but had no effect on SOD activity in cortex.Conclusions Rosiglitazone has a neuroprotective role against streptozotocin-induced cognitive impairment and associated oxidative/nitrative stress.