Apelin-13 Impairs Reconsolidation Of Novel Object Recognition Memory By Down-regulating CAMP-Lactate Pathway In Rats

[Objective] The formation of long-term memory usually involves several phases,including memory acquisition,consolidation,reconsolidation,and retrieval.Apelin and its receptor APJ are highly distributed in the central nervous system,especially in the hippocampus,which is closely related to learning and memory.We have reported that Apelin-13 impairs the process of memory consolidation in the novel objection recognition(NOR)task.However,the effect of Apelin-13 on the reconsolidation of NOR memory is still unclear.This study mainly explored the effect of Apelin-13 on the reconsolidation of NOR memory in rats and its possible mechanism.[Methods] Experiment 1 was designed to examined the effect of intracerebroventricular(i.c.v.)microinjection of Apelin-13 on NOR memory reconsolidation in rats.The NOR test is mainly involved three phases,training(day 1),reactivation(day 2),and test(day 3).Immediately after reactivation of the NOR test(0h),6h or instead of reactivation,rats were received i.c.v.injection of vehicle or Apelin-13 at the corresponding time point,and the total exploration time of both objects during the training and reactivation phase and the discrimination index of the test phase were observed and recorded;And the number of crossing grids in the test chamber during test phase was recorded to evaluate the spontaneous exercise ability of the rats.Experiment 2 was designed to examined whether the cAMP-L-lactate pathway mediates the impairment of Apelin-13 on NOR memory reconsolidation of rats.The effects of i.c.v.injection of aperin-13 on cAMP and L-lactate level in hippocampus of rats and the effect of cAMP analogue 8-Br-cAMP on Apelin-13 in reducing hippocampal L-lactate levels was measured by Elisa kit.The effects of i.c.v.injection of 8-Br-cAMP and L-lactate on NOR memory reconsolidation in rats impaired by Apelin-13 were observed.[Results] Experiment 1: In the training and the reactivation phase,there was no significant difference between the groups in the total exploration time of both objects.In the test phase,i.c.v.injection of Apelin-13 immediately after memory reactivation significantly decreased the rat discrimination index,and 6 hours after reactivation or without reactivation,only injected Apelin-13 at the corresponding time point did not affect the discrimination index of rats.In addition,Apelin-13 did not affect the ability of spontaneous exercise in rats.Experiment 2: The i.c.v.injection of Apelin-13 significantly decreased the levels of cAMP and L-lactate in the hippocampus of rats;the i.c.v.injection of 8-Br-cAMP reversed the decreased level of L-lactate by Apelin-13 in the hippocampus of rats.The i.c.v.injection of 8-Br-cAMP and L-lactate reversed the damage effect of Apelin-13 on NOR memory reconsolidation in rats.[Conclusion] Apelin-13 impairs NOR memory reconsolidation by down-regulating cAMP-Lactate pathway in rats.