Adenosine monophosphate activated protein kinase (AMPK) is essential for the memory improving effect of adiponectin

Neurosci Lett. 2021 Apr 1;749:135721. doi: 10.1016/j.neulet.2021.135721. Epub 2021 Feb 11.


Adiponectin (APN) plays a major role in the regulation of insulin sensitivity and glucose homeostasis. Insulin and APN have a positive effect on memory. In this study, we examined whether the inhibition of AMPK could block the memory improving effect of APN or affect the IRS1 expression. Animal model of AD was developed by intracerebroventricular (icv) injection of 3 mg/kg streptozotocin (STZ), in 12 weeks old Wistar rats, on days 1 and 3 after cannulation. Dorsomorphin (DM) and APN (600 nM) were injected 30 and 20 min before the acquisition phase, respectively. DM was applied in 3 different doses (0.2, 2 and 20 μM). All behavioral tests were performed on days 15 and 16; the Preference Index (PI) was calculated for novel object recognition (NOR) test, while the step through latency (STL) and total time in dark compartment (TDC) were recorded and analyzed for the passive avoidance task. Relative expression of insulin receptor substrate-1 (IRS-1) protein in the hippocampus was measured by western blotting. In early retrieval test, STZ + APN treatment increased STL (P < 0.0001) and decreased TDC (P < 0.05) in comparison to STZ group, while STZ + APN + DM (2μM) caused a decrease in STL (P < 0.05) and increase in TDC (0.2μM and 2μM DM; P < 0.05). Icv injection of DM (0.2μM and 2μM) before APN decreased the PI significantly (P < 0.05) in comparison to STZ + APN group. APN treatment raised the IRS-1 expression and DM reversed this increment, significantly (P < 0.0001). It is concluded that the memory improving effect of APN is mediated, at least in part, by the AMPK pathway. APN is also able to boost insulin signaling by overexpression of IRS-1 in the hippocampus.

Keywords: AMPK; Adiponectin; Dementia; Dorsomorphin; Insulin receptor substrate.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AMP-Activated Protein Kinases / drug effects*
  • AMP-Activated Protein Kinases / metabolism
  • Adenosine Monophosphate / pharmacology*
  • Adiponectin / pharmacology*
  • Alzheimer Disease / drug therapy
  • Animals
  • Disease Models, Animal
  • Male
  • Memory / drug effects*
  • Memory Disorders / drug therapy
  • Rats, Wistar
  • Signal Transduction / drug effects


  • Adiponectin
  • Adenosine Monophosphate
  • AMP-Activated Protein Kinases