Cognitive dysfunction associated with diabetic ketoacidosis in rats

Background: Type 1 diabetes mellitus in children may be associated with neurocognitive deficits of unclear cause. A recent retrospective study in children suggested possible associations between diabetic ketoacidosis (DKA) and decreased memory. The current investigation was undertaken to determine whether cognitive deficits could be detected after a single episode of DMA in an animal model. Methods: Streptozotocin was used to induce diabetes in juvenile rats, and rats were then treated with subcutaneous insulin injections. In one group, insulin was subsequently withdrawn to allow development of DMA, which was then treated with insulin and saline. After recovery from DKA, subcutaneous insulin injections were re-started. In the diabetes control group, rats continued to receive subcutaneous insulin and underwent sham procedures identical to the DMA group. One week after recovery, cognitive function was tested using the Morris Water Maze, a procedure that requires rats to locate a hidden platform in a water pool using visual cues. During a 10 day period, mean time to locate the platform (latency) during 4 trials per day was recorded. Results: Comparison of latency curves demonstrated longer mean latency times on days 7 and 8 in the DKA group indicating delayed learning compared to diabetic controls. Conclusions: These data demonstrate that a single DMA episode results in measurable deficits in learning in rats, consistent with findings that DMA may contribute to neurocognitive deficits in children with type 1 diabetes. (C) 2012 Elsevier Ireland Ltd. All rights reserved.