Effect Of Pioglitazone On The Learning Memory And Glycogen Synthase Kinase-3β,tau Protein Phosphorylation In Model Of AD Rats

Objective:To investigate the effect of Pioglitazone on the learning memory and glycogensynthase kinase-3β,tau protein phosphorylation in model of Alzheimer's disease rats, andexplore the therapeutical effect on AD rats and the potential mechanism of action ofPioglitazone.Methods:1. Establishment of AD rats model. Okadaic acid (OA) was injected into the hippocampus CA1region overnight, four times totally.2. Pioglitazone made suspension to intragastric administration; the rats were measured bloodglucose.3. Behavior was tested by the Morris water maze.4. Research the relationship between GSK-3βand tau protein phosphorylation. The GSK-3βandtau protein hyperphosphorylation were detected by immunohistochemistry staining.Results:1. Determination of peripheral blood glucose: blood glucose of rats compared with before andafter using medicine were no significant difference(P>0.05).2. The Morris water maze test manifested: compared with the control group, the model grouprats have longer escape latency(P<0.05), moreover, the percentage of terrace quadrantswimming path length occupying total path length is the shorter than the control group(P<0.05);compared with the model group, low and high dose of Pioglitazone group rats have shorterescape latency(P<0.05), the percentage of terrace quadrant swimming path length occupyingtotal path length is the longer than the model group(P<0.05), but there is no significantdifference between two groups rats(P>0.05).3. The activity of GSK-3β: compared with the control group, the model group rats haveobviously positive cells, the grey scale is lower(P<0.05); compared with the model group, lowand high dose of Pioglitazone group rats have not obviously positive cells, the grey scale ishigher(P<0.05), but there is no significant difference between two groups(P>0.05).4. The activity of tau protein phosphorylation: compared with the control group, the model grouprats have obviously positive cells, the grey scale is lower(P<0.05); compared with the modelgroup, low and high dose of Pioglitazone group rats have not obviously positive cells, the grey scale is higher(P<0.05), but there is no significant difference between two groups(P>0.05).Conclusion:1. AD rats were successfully induced by injected OA into the hippocampus CA1 region.2. Pioglitazone can improve the learning and memory ability of AD rats, it may reduce tauprotein phosphorylation by reducing the activity of GSK-3β, AD may be related with insulinsignal transduction.3. Pioglitazone is effective for AD rats, moreover it provide a new idea for Alzheimer's disease.