The disturbance of hippocampal CaMKII/PKA/PKC phosphorylation in early experimental diabetes mellitus

CNS Neurosci Ther. 2013 May;19(5):329-36. doi: 10.1111/cns.12084. Epub 2013 Mar 14.

Abstract

Background: Defining the impact of diabetes and related risk factors on brain cognitive function is critically important for patients with diabetes.

Aims: To investigate the alterations in hippocampal serine/threonine kinases signaling in the early phase of type 1 and type 2 diabetic rats.

Methods: Early experimental diabetes mellitus was induced in rats with streptozotocin or streptozotocin/high fat. Changes in the phosphorylation of proteins were determined by immunoblotting and immunohistochemistry.

Results: Our data showed a pronounced decrease in the phosphorylation of Ca(2+) /calmodulin-dependent protein kinase II (CaMKII) in the hippocampi of both type 1 and type 2 diabetic rats compared with age-matched control rats. Unexpectedly, we found a significant increase in the phosphorylation of synapsin I (Ser 603) and GluR1 (Ser 831) in the same experiment. In addition, aberrant changes in hippocampal protein kinase C (PKC) and protein kinase A (PKA) signaling in type 1 and type 2 diabetic rats were also found. Moreover, PP1α and PP2A protein levels were decreased in the hippocampus of type 1 diabetic rats, but significantly up-regulated in type 2 diabetic rats.

Conclusions: The disturbance of CaMKII/PKA/PKC phosphorylation in the hippocampus is an early change that may be associated with the development and progression of diabetes-related cognitive dysfunction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2 / metabolism*
  • Cyclic AMP-Dependent Protein Kinases / metabolism*
  • Diabetes Mellitus, Experimental / metabolism*
  • Hippocampus / metabolism*
  • Male
  • Phosphorylation
  • Protein Kinase C / metabolism*
  • Protein Phosphatase 1 / analysis
  • Protein Phosphatase 2 / analysis
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, AMPA / metabolism
  • Streptozocin
  • Synapsins / metabolism

Substances

  • Receptors, AMPA
  • Synapsins
  • Streptozocin
  • Cyclic AMP-Dependent Protein Kinases
  • Protein Kinase C
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2
  • Protein Phosphatase 1
  • Protein Phosphatase 2
  • glutamate receptor ionotropic, AMPA 1