A novel role for the calcium sensing receptor in rat diabetic encephalopathy

Cell Physiol Biochem. 2015;35(1):38-50. doi: 10.1159/000369673. Epub 2015 Jan 2.


Background: Diabetic encephalopathy is a common complication of diabetes, and it may be involved in altering intracellular calcium concentrations ([Ca(2+)]i) at its onset. The calcium sensing receptor (CaSR) is a G-protein coupled receptor, however, the functional involvement of CaSR in diabetic encephalopathy remains unclear.

Methods: In this study, diabetic rats were modeled by STZ (50 mg/kg). At the end of 4, 8 and 12 weeks, the CaSR expression in hippocampus was analyzed by Western blot. In neonatal rat hippocampal neurons, the [Ca(2+)]i was detected by laser scanning confocal microscopy, the production of reactive oxygen species (ROS) in mitochondria, the level of NO and the mitochondrial transmembrane potential were measured by MitoSOX, DAF-FM and JC-1, respectively.

Results: Our results showed in hippocampal neurons treated with high glucose, CaSR regulated [Ca(2+)]i through the PLC-IP3 pathway. CaSR expression was decreased and was involved in the changes in [Ca(2+)]i. Mitochondrial membrane potential, NO release and expression of p-eNOS decreased, while the production of ROS in mitochondria increased.

Conclusion: Down-regulation of CaSR expression was accompanied by neuronal injury, calcium disturbance, increased ROS production and decreased release of NO. Up-regulation of CaSR expression attenuated these changes through a positive compensatory protective mechanism to inhibit and delay diabetic encephalopathy in rats.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / metabolism
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2 / metabolism
  • Cells, Cultured
  • Diabetes Mellitus, Experimental / chemically induced
  • Diabetes Mellitus, Experimental / metabolism
  • Diabetes Mellitus, Experimental / pathology*
  • Down-Regulation / drug effects
  • Glucose / pharmacology
  • Hippocampus / metabolism
  • Male
  • Membrane Potential, Mitochondrial / drug effects
  • Mitochondria / metabolism
  • Neurites / physiology
  • Neurons / cytology
  • Neurons / drug effects
  • Neurons / metabolism*
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase Type III / metabolism
  • Rats
  • Rats, Wistar
  • Reactive Oxygen Species / metabolism
  • Receptors, Calcium-Sensing / metabolism*
  • Streptozocin / toxicity


  • Reactive Oxygen Species
  • Receptors, Calcium-Sensing
  • Nitric Oxide
  • Streptozocin
  • Nitric Oxide Synthase Type III
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2
  • Glucose
  • Calcium