Effect of intracerebroventricular administration of dorsomorphin and adiponectin on memory in experimental model of Alzheimer s disease

Background and Aim : There is a close relationship between Alzheimer s disease (AD) and insulin signaling dysfunction. Adiponectin (APN) is an adipocytokine that increases insulin sensitivity through binding to its receptors (AdipoR 1, AdipoR2). Adiponectinase signaling is via AMPK and PPAR-α. Given the role of APN in decreasing insulin resistance and memory improvement; we investigated the probable signaling pathway involved in memory improvement by APN in the experimental model of Alzheimer s disease.Methods : Fifty-six adult male rats were randomly allocated to 7 groups: control, APN, STZ, STZ+APN and DM in three doses (0.2, 2 and 20 μM). ). On days 1 and 3, rats received STZ (3 mg/kg, icv) and were assessed by passive avoidance task and novel object recognition test, after 2 weeks. Thirty minutes before retrieval tasks, APN or APN+DM were injected, intracerebroventricularly.Results : The step through latency (STL), which was diminished by STZ, increased significantly (P 0.0001) in APN+STZ group. Administration of different doses of DM before APN, reversed the memory improving effect of APN to a significant level (P 0.01). Total time spent in the dark compartment (TDC) was decreased by APN, while DM increased the TDC values to a significant level (P 0.01). In the cognitive memory test, the preference index (PI) decreased significantly in the APN+STZ+DM groups (P 0.01).Conclusion : Our results indicate that adiponectin is able to compensate the STZ-induced cognitive decline, probably by boosting the insulin signaling pathway. In fact, DM inhibited the ameliorative effect of adiponectin by inhibiting AMPK. Thus, adiponectin improves memory probably by AMPK phosphorylating and regulation of energy metabolism.

Keywords:

Alzheimer s disease , Adiponectin , AMP kinase , Memory , Streptozotocin