861-P: The Effect of Dual Amylin and Calcitonin Receptor Agonist Treatment on Spatial Memory in Rat Models of Metabolic Syndrome

Abstract

Obesity and metabolic-related complications, especially insulin resistance, have been linked to cognitive dysfunction. Dual amylin and calcitonin receptor agonists (DACRAs) elicit beneficial effects on body weight, glucose control, and insulin action, making them novel candidates for treating obesity and related comorbidities. Whether DACRAs affect cognition has yet to be addressed. With these studies, we evaluated the effect of DACRA treatment on spatial learning and memory in rat models of metabolic syndrome. Spatial learning and spatial memory retention were evaluated by Morris Water Maze in ZDSD rats treated with KBP-336 (4.5 nmol/kg Q3D) for 7 months and ZSF1 rats treated with KBP-336 (4.5 nmol/kg Q3D) for 2 months. In the ZDSD study, rats performed 8 training trials with a hidden platform in a constant position and a 60 s probe without the platform. At the study end, rats performed a 60 s probe followed by 4 re-training trials and another probe. At study end of the ZSF1 study, rats performed 6 training trials with a hidden platform in a constant position followed by a 60 s probe without the platform. In both studies, KBP-336 treatment improved the overall metabolic status, including glucose control and insulin action. In ZDSD rats, KBP-336-treated rats spent more time and traveled longer distances in Whishaw's corridor than vehicle-treated rats during the probes at the study end. Together indicating a possible treatment improvement in spatial memory on KBP-336. In ZSF1 rats, KBP-336 treatment resulted in increased time spent in the platform quadrant and Whishaw's corridor, as well as increased distance, traveled in Whishaw's corridor during the probe. In both studies, the treatment did not affect the spatial learning evaluated as latency to reach the hidden platform during the training trials. Altogether, we found that the improved metabolic status obtained with KBP-336 treatment might have a beneficial effect on spatial memory in diabetic and obese rat models. Disclosure K.Mohamed: Employee; Nordic Bioscience. A.T.Larsen: Employee; Nordic Bioscience A/S. S.A.Melander: None. M.A.Karsdal: Speaker's Bureau; Pfizer Inc. K.Henriksen: Employee; Nordic Bioscience A/S, Stock/Shareholder; Nordic Bioscience A/S. Funding Danish Research Foundation; Innovation Fund Denmark; European Union’s Horizon 2020 Research and Innovation Program (814244)