Title:Intracerebroventricular Injection of MHY1485 Blocked the Beneficial
Effect of Adiponectin on Aversive Memory in the STZ Model of Dementia
Volume: 23
Issue: 3
Author(s): Samira Rashtiani, Iran Goudarzi, Adele Jafari and Kambiz Rohampour*
Affiliation:
- Department of Physiology, Neuroscience Research Center,
Guilan University of Medical Sciences, Rasht, Iran
Keywords:
Alzheimer’s disease, adiponectin, mammalian target of rapamycin (mTOR), MHY1485, memory, dementia.
Abstract:
Background: The most prominent adipokine, adiponectin (APN), has an adverse relationship
with the malfunction of adipose tissue. Obesity causes a decrease in plasma APN levels,
which eventually results in insulin resistance and diabetes. In this study, we assessed how the effects
of APN on memory are influenced by the insulin receptor substrate-1 (IRS-1) and the mammalian
target of rapamycin (mTOR) pathways.
Methods: Streptozotocin (STZ) 3 mg/kg intracerebroventricular injections on days 1 and 3 following
cannulation were used to create an animal model of Alzheimer's disease. The acquisition phase
was preceded by injections of MHY and adiponectin. For the passive avoidance task, the stepthrough
latency and total duration in the dark compartment were recorded and evaluated, and the
preference index was calculated for the novel object identification test. IRS-1 protein expression in
the hippocampus was assessed by western blotting.
Results: STZ reduced the step-through latency (STL), which rose significantly (P≤0.001) in the
APN+STZ group. The memory-improving effects of APN were reversed when MHY was administered
first (P≤0.001). The STZ and APN+STZ+MHY groups both had a substantial decline in the
preference index (P≤0.01). Compared to the control group, the STZ group's expression of the IRS-
1 protein was dramatically reduced (P≤0.0001). In contrast to the APN+STZ group, the MHYtreated
group likewise showed decreased IRS-1 protein expression (P≤0.0001), but APN+STZ was
able to enhance IRS-1 expression rate (P≤0.0001).
Conclusion: In a rat model of AD, we found that adiponectin improved aversive and cognitive
memory, which is at least partially mediated by the mTOR signaling cascade.
