Antidepressant Effect Of Lactate And Its Mechanism Of CAMP-BDNF Pathway

object:Recent studies have found that peripheral injection of lactate can produce antidepressant effect,but its characteristics and mechanisms are unclear.Based on the forced swimming model of rats,this study observed the dose and time effect characteristics of antidepressant effect of injection of lactate into lateral ventricles;moreover from the perspective of cAMP-BDNF pathway,explored the neuromolecular mechanism of antidepressant effect of lactate,providing new ideas for the prevention and treatment of depression.Methods : Adult male SD rats were catheterized in the lateral ventricle and recovered for 1 week.Depression-like behavior of rats was evaluated by immobility time of Forced Swimming Test(FST),spontaneous activity was evaluated by spontaneous activity test,cAMP level in hippocampus was detected by ELISA method,and BDNF expression level in hippocampus was detected by Western Blot method.Results:1.A single injection of 100 nmol lactate(L-lactate)into the lateral ventricle significantly reduced the immobility time in the FST test in rats,while 50 and 200 nmol lactate had no such effect;lactate did not affect the spontaneous activity of rats.2.After a single injection of 100 nmol of lactate into the lateral ventricle,the immobility time in the FST test in rats was significantly reduced after 1 h,24 h,3 d,and 7 d,but there was no such effect in 0.5 h after injection.3.A single injection of D-lactate,L-pyruvate,and D-glucose with a single caloric value of 100 nmol lactate in the lateral ventricle did not affect the immobility time in the FST.4.The protein synthesis inhibitor anisomycin significantly blocked the antidepressant effect of lactate,while the RNA polymerase inhibitor antinomycinD had no such effect.5.Lactate rapidly up-regulated cAMP and BDNF levels in rat hippocampals.6.Adenylate cyclase inhibitor SQ22536 significantly blocked the up-regulation of lactate on hippocampal cAMP and BDNF levels and the antidepressant effect of lactate.7.The TrkB inhibitor ANA-12 significantly blocked the antidepressant effect of lactate.Conclusion:1.Lactate produces antidepressant effect depended on the dose and time,and the antidepressant effect has persistent characteristics;2.cAMP-BDNF pathway mediates the antidepressant effect of lactate.