title: A novel role for the calcium sensing receptor in rat diabetic encephalopathy.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pathophysiology, Harbin Medical University, Harbin, China.
authors.forename: Shiyun
authors.initials: S
authors.lastname: Dong
authors.forename: Gang
authors.initials: G
authors.lastname: Li
authors.forename: Dan
authors.initials: D
authors.lastname: Zheng
authors.forename: Jichao
authors.initials: J
authors.lastname: Wu
authors.forename: Dianjun
authors.initials: D
authors.lastname: Sun
authors.forename: Fan
authors.initials: F
authors.lastname: Yang
authors.forename: Xiangjing
authors.initials: X
authors.lastname: Yu
authors.forename: Ting
authors.initials: T
authors.lastname: Li
authors.forename: Aili
authors.initials: A
authors.lastname: Sun
authors.forename: Jiaqi
authors.initials: J
authors.lastname: Liu
authors.forename: Xin
authors.initials: X
authors.lastname: Zhong
authors.forename: Changqing
authors.initials: C
authors.lastname: Xu
authors.forename: Fanghao
authors.initials: F
authors.lastname: Lu
authors.forename: Weihua
authors.initials: W
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D015536:Down-Regulation / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology; D006624:Hippocampus / Q000378:metabolism; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000378:metabolism; D016501:Neurites / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D044169:Receptors, Calcium-Sensing / Q000378:metabolism*; D013311:Streptozocin / Q000633:toxicity
chemical_list: D017382:Reactive Oxygen Species; D044169:Receptors, Calcium-Sensing; D009569:Nitric Oxide; D013311:Streptozocin; D052250:Nitric Oxide Synthase Type III; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D005947:Glucose; D002118:Calcium