Therapeutic Effects Of Combined and Chronic Treatment of Tat-GluA23y and D-Serine on Cognitive Dysfunction in Postmenopausal Rats.

Background: The incidence of Alzheimer's disease (AD) in female gender compared with male has been addressed as a health concern, particularly in menopausal age. We here hypothesized that co-administration of NMDARs agonist (D-serine) and AMPARs endocytosis inhibitor (Tat-GluA23y) might be a potential target for alleviating memory impairment in sporadic Alzheimer model of rats.

Methods: Forty-eight female Wistar rats weighing 200-220 randomly divided into six groups. One month later, ovariectomized rats underwent stereotaxic surgery and were cannulated into the brain lateral ventricles. Streptozotocin was injected (3 mg/kg), then animals received the related treatments until the day 51, which experienced acquisition of spatial memory in Morris Water Maze test. Finally, the level of phosphorylated cAMP response element binding protein (CREB) in the hippocampus was measured by Western blotting.

Results: Co-administration of D-serine and GluA23y significantly enhanced the acquisition and retrieval of impaired spatial memory in ovariectomized rats with AD (p < .001). Compared to Glu-A 23, D-serine caused more improvement in the mentioned parameters above, however, these values for both groups were still significantly different from the control group (P < .05).

Conclusion: Simultaneous treatment with D-serine and GluA23y synergistically improved STZ induced spatial memory impairment in OVX rat, probably partly via increase in phosphorylated CREB protein.