Kisspeptin-13’s effect on spatial learning and memory in a rat model of Alzheimer\’s disease

01/30/2020

Éva Dobó¹, Katalin Ibos¹, Júlia Szakács¹, Zsolt Bagosi¹, Krisztina Csabafi¹

¹ Department of Pathophysiology Faculty of Medicine University of Szeged, Szeged

The Hypothalamic-pituitary-gonadal (HPG) axis may affect the development and progression of Alzheimer's disease (AD). A regulator of the HPG system is kisspeptin (Kp) that also modifies the expression of antioxidant enzymes. Kp and its receptors are expressed in many regions of the central nervous system, such as the hypothalamus, amygdala and the dentate gyrus of the hippocampus. Previously, the role of Kp has been investigated in AD as well as in learning processes. In fact, Kp can bind the Amyloid-B (A) peptide in vitro and facilitate the consolidation of passive avoidance learning in mice. The aim of this study was to investigate the effect of Kp-13 on spatial learning and memory in A(1-42) induced neurotoxicity. 6-week-old male and female Wistar rats were used in our experiments. First, intracerebroventricular cannula were implanted, then A in a dose of 4µg/4µl was injected. After a recovery time, spatial memory was tested by Morris Water Maze (MWM) tests. Afterwards, the hippocampi were isolated and the Kp-13 (1µg/1ml) induced Acetylcholine (ACh) release was measured via a superfusion system. Finally, hippocampi and prefrontal cortexes were isolated, and expression of c-Fos and Egr-1 gene levels were determined by RT-PCR.Results showed that compared to the control group, A treatment significantly decreased the learning ability of rats. This effect was blunted by Kp-13 treatment in females. The superfusion study revealed that AD hippocampal slices secreted significantly less ACh then the control and this was blunted by Kp-13. Finally, Kp-13 was shown to inhibit A induced Egr-1 gene expression. Acknowledgements: EFOP-3.6.2-16-2017-00006