The effect and mechanism of adropin on learning

Objective: In our study, we aimed to investigate the effects of adropin applied to the lateral ventricle on spatial learning and memory and its molecular mechanisms. Method: Thirty male Sprague Dawley rats were randomly divided into two experimental groups as control and adropin groups. The control group received 0.9% NaCl solution (icv injections for six days) and the adropin group received 1 nmol of adropin (icv injections for six days) dissolved in 0.9 % NaCl solution. The Morris water maze, Y-maze and object location recognition tests were performed to evaluate learning and memory and the locomotor activity tests were measured to assess the motor functions. The expression of Akt, p-Akt, CREB, p-CREB, MAPK, p-MAPK, GSK3β, p-GSK3β, BDNF and NMDA receptor NR2B subunit were determined by using western blot. The levels of adropin, glutamine-glutamic acid were measured by an ELISA kit and mass spectrometry, respectively. Results: The locomotor activity parameters were elevated with adropin administration in comparison to the control group. The adropin-injected group showed better performance in the spatial memory tasks as compared to the control group. In addition, adropin administration increased the levels of p-Akt, p-CREB and BDNF expression. We observed that p-MAPK/MAPK ratio and GSK3β expression did not change in the adropin group with respect to the control group. Moreover, a significant alteration of NR2B expression was not observed in the adropin group. The glutamine, glutamic acid and adropin levels were found to increase with adropin treatment in the hippocampal tissues. Conclusion: The result of the present study has shown that adropin improves spatial memory and learning of adult rats in the Morris Water Maze, Y-maze, and object location recognition tests. The adropin-induced improvements appear to be stimulated the Akt/CREB/BDNF signaling in the hippocampus. Key words: adropin, learning, memory, CREB, BDNF