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Acceleration of Lactate Uptake and Utilization Contributes to Neuroprotective Action of FGF21 Involved in Naturally Aging Mice - PubMed

11 hours ago
  • #neuroprotection
  • #FGF21
  • #lactate metabolism
  • FGF21 plays a neuroprotective role in aging mice by enhancing lactate uptake and utilization.
  • Aging mice show upregulated neuronal FGF21 expression and increased astrocyte-neuron lactate shuttle (ANLS) rate in hippocampal and cortical regions.
  • Exogenous FGF21 administration improves learning, memory, and lactate metabolism in aging mice via MCT2 dependency.
  • HCA1-KO mice show abolished CREB and MAPK signaling activation in lactate-infused mice, differing from aging mice.
  • In vitro studies confirm p38-mediated FGF21 production and PI3K-mTOR-dependent MCT2 protein translation in aging.
  • Increased FGF21 levels may help neurons combat age-related neuroinflammation and lactate accumulation.
  • Lactate shuttle rate and microenvironment are linked to neuronal function, suggesting a therapeutic target for aging-related cognitive dysfunction.