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

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.

• Authors: Mei-Hua Liao, Ying-Chun Xiang, Ji-Yun Huang, Rong-Rong Tao, Yun Tian, Wei-Feng Ye, Gen-Sheng Zhang, Ying-Mei Lu, Muhammad M Ahmed, Zhi-Rong Liu, Kohji Fukunaga, Feng Han
• Journal: CNS neuroscience & therapeutics (CNS Neurosci Ther) Vol. 19 Issue 5 Pg. 329-36 (May 2013) ISSN: 1755-5949 [Electronic] England
• PMID: 23490331 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2013 Blackwell Publishing Ltd.

Chemical References

• 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

Topics

• 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)