JIANG Haowei,YI Qingqing,SHEN Danjie, et al. The effect of FGF21 on learning and memory impairment induced by lactate accumulation in mice and its mechanism[J]. JOURNAL OF WEZHOU MEDICAL UNIVERSITY, 2021, 51(12): 947-953.
Abstract：Objective: To study whether fibroblast growth factor 21 (FGF21) can improve learning and memory impairment induced by lactate accumulation in mice and its potential mechanism. Methods: Male mice were randomly divided into three groups: control group, lactate group and lactate+FGF21 group. Y maze, Morris water and real-time quantitative PCR was used respectively to explore the learning and memory ability in different groups of mice. The specific metabolic changes of hippocampus were investigated by nuclear magnetic resonance based metabonomics methods. Results: The lactate group showed lower spontaneous exchange rate of Y maze, longer escape latency and shorter crossing platform, compared with the controls. The level of synaptic plasticity genes, including early growth response-1 (EGR-1), proto-oncogene (c-Fos), presynaptic (SYP) and postsynaptic proteins (PSD) (including PSD-93, PSD-95) mRNA level were significantly decreased in lactate group mice (P<0.05). FGF21 could restore the decline trend of learning and memory caused by lactate treatment(P<0.05). Metabonomic data showed taurine, inosine, creatine, inositol, glutathione, γ-aminobutyric acid,succinate, N-acetylaspartate, adenosine monophosphate and inosine acid decreased significantly in hippocampal extracts from the lactate mice, while their contents increased significantly after FGF21 treatment (P<0.05).Conclusion: FGF21 might improve the learning and memory dysfunction of mice by promoting lactate utilization,through restoring ATP-dependent energy metabolism pathways and NADH-related oxidative stress pathways.
