The Disturbance of Hippocampal CaMKII/PKA/PKC Phosphorylation in Early Experimental Diabetes Mellitus

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

Research output: Contribution to journalArticlepeer-review

23 Citations (Scopus)

Abstract

Summary: 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 Ca2+/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.

Original languageEnglish
Pages (from-to)329-336
Number of pages8
JournalCNS Neuroscience and Therapeutics
Volume19
Issue number5
DOIs
Publication statusPublished - 2013 May

Keywords

  • Brain
  • CaMKII
  • Diabetes
  • Hippocampus
  • PKA
  • PKC
  • Phosphorylation

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health
  • Physiology (medical)
  • Pharmacology (medical)

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