Fish oil modulates glycogen synthase kinase-3 signaling pathway in diabetes-induced hippocampal neurons apoptosis

Brain Res. 2014 Jul 29:1574:37-49. doi: 10.1016/j.brainres.2014.05.050. Epub 2014 Jun 9.


Previous research has demonstrated that diabetes induces learning and memory deficits. However, the mechanism of memory impairment induced by diabetes is poorly understood. Dietary fatty acids, especially polyunsaturated fatty acids, have been shown to enhance learning and memory and prevent memory deficits in various experimental conditions. The present study investigated the effects of fish oil supplementation on the neuron apoptosis in the hippocampus of streptozotocin (STZ)-induced diabetes rats, further explored the effect of fish oil on the phosphorylation of protein kinase B and glycogen synthase kinase-3 beta. The effects of diabetes and fish oil treatment on the spatial learning and memory were also evaluated using the Morris Water Maze. STZ-induced diabetes impaired spatial learning and memory of rats, which was associated with the apoptosis of hippocampal neurons and oxidative stress. Fish oil administration ameliorated cognitive deficit, reduced oxidative stress, increased AKT phosphorylation, decreased GSK-3β phosphorylation, and decreased pro-apoptotic molecules expression, which protected the hippocampal neurons from apoptosis in diabetic rats. These results suggested a potential role for fish oil as an adjuvant therapy for the prevention and treatment of diabetic complications.

Keywords: Apoptosis; Cognitive impairments; Diabetes; Fish oil; GSK-3β; PKB/AKT.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / physiology*
  • Blood Glucose / metabolism
  • Diabetes Mellitus, Experimental / diet therapy*
  • Diabetes Mellitus, Experimental / enzymology
  • Diabetes Mellitus, Experimental / pathology
  • Dietary Supplements
  • Fish Oils / administration & dosage*
  • Glycogen Synthase Kinase 3 / metabolism*
  • Glycogen Synthase Kinase 3 beta
  • Hippocampus / enzymology*
  • Hippocampus / pathology
  • Male
  • Maze Learning
  • Neurons / enzymology*
  • Neurons / pathology
  • Oxidative Stress / physiology
  • Phosphorylation
  • Proto-Oncogene Proteins c-akt / metabolism
  • Random Allocation
  • Rats, Sprague-Dawley
  • Signal Transduction
  • Spatial Memory / physiology


  • Blood Glucose
  • Fish Oils
  • Glycogen Synthase Kinase 3 beta
  • Gsk3b protein, rat
  • Proto-Oncogene Proteins c-akt
  • Glycogen Synthase Kinase 3