Adiponectin Attenuates Streptozotocin-Induced Tau Hyperphosphorylation and Cognitive Deficits by Rescuing PI3K/Akt/GSK-3β Pathway

Neurochem Res. 2018 Feb;43(2):316-323. doi: 10.1007/s11064-017-2426-2. Epub 2017 Nov 2.

Abstract

Clinical studies have demonstrated that decreased adiponectin is associated with the development of Type 2 diabetes mellitus (T2DM) and Alzheimer's disease (AD). We focused on determining the neuroprotective effect offered by adiponectin against streptozotocin-induced brain damage in ICV-STZ rat model. We found that adiponectin supplements significantly restored the cognitive deficits in ICV-STZ rat model including shorter escape latency, more crossing times and increased time spent in the target quadrant. Adiponectin supplements also increased number of dendritic branches and mushroom percentage. In addition, adiponectin supplements attenuated tau hyperphosphorylation at multiple AD-related sites through activation of protein Ser9-phosphorylated glycogen synthase kinase-3β (Ser9-GSK-3β) with increased the Akt and PI3K activity. Our data suggest that adiponectin supplements have neuroprotective effects on the ICV-STZ rat model, which may be mediated by the activation of the PI3K/Akt/GSK-3β signaling pathway.

Keywords: Adiponectin; Alzheimer’s disease; Glycogen synthase kinase-3β.

MeSH terms

  • Adiponectin / pharmacology*
  • Animals
  • Cognition Disorders / drug therapy
  • Glycogen Synthase Kinase 3 beta / drug effects*
  • Glycogen Synthase Kinase 3 beta / metabolism
  • Male
  • Neurons / drug effects
  • Neurons / metabolism
  • Neuroprotective Agents / pharmacology
  • Phosphatidylinositol 3-Kinases / drug effects
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphorylation / drug effects
  • Proto-Oncogene Proteins c-akt / drug effects
  • Proto-Oncogene Proteins c-akt / metabolism
  • Rats, Sprague-Dawley
  • Streptozocin / pharmacology*
  • tau Proteins / metabolism
  • tau Proteins / pharmacology*

Substances

  • Adiponectin
  • Neuroprotective Agents
  • tau Proteins
  • Streptozocin
  • Phosphatidylinositol 3-Kinases
  • Glycogen Synthase Kinase 3 beta
  • Proto-Oncogene Proteins c-akt