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The expression of calcium/calmodulin-dependent protein kinase II in spinal cord in rat models of type 1 and type 2 diabetes

Introduction: Diabetic neuropathy is one of the most common complications of the diabetes. The activation of calcium/calmodulin-dependent protein kinase II (CaMKII) has been suggested as a key player in chronic pain development. Therefore, the aim of this study was to investigate the expression of CaMKII in the dorsal horn of spinal cord in early model of DM type 1 and type 2. Methods: Sprague-Dawley rats (n=40) were used. DM1 model was induced after overnight fasting with 55 mg/kg of streptozotocin (STZ) and DM2 model using combination of high-fat diet and low-dose STZ. Pure citrate buffer solution was intraperitoneally injected to control rats for DM1and DM2. Rats were sacrificed two weeks and two months after diabetes induction. The expression of total CaMKII and its alpha isoform in dorsal horn was quantified using immunohistochemistry. Results: Increased expression of tCaMKII and pCaMKIIα was seen in dorsal horn of DM1 animals 2 weeks and 2 months after diabetes induction. In DM2 animal model, similar change in the expression of tCaMKII and pCaMKIIα was visible after 2 weeks, but not after two months. The expression of pCaMKIIα was pronounced the most in laminae I-III. Difference in the IB4 expression was not observed between groups. Discussion: Studies has shown increased expression of CaMKII in dorsal root ganglia in rat models of DM1 and DM2 two weeks and two months after diabetes induction. Changes in the CaMKII expression were also observed in DRG and dorsal horn six months and one year following induction of DM1. However, the expression pattern of CaMKII in dorsal horn in early diabetes has not been reported yet. Conclusion: The observed changes in the expression of CaMKII and its alpha isoform may be involved in the neuropathic pain development early in DM1, but not in DM2. CaMKII may be a suitable target for diabetic pain treatment.

diabetic neuropathy; CaMKII; spinal cord; dorsal horn

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