Exercise-Induced Lactate Release Mediates Mitochondrial Biogenesis in the Hippocampus of Mice via Monocarboxylate Transporters.
Level 5 - mechanism / opinion, no new human data
Preclinical animal research in mice
PubMed 34603087 · doi:10.3389/fphys.2021.736905
What was done
The authors evaluated whether an acute bout of exercise (low-, moderate-, or high-intensity) induces hippocampal mitochondrial biogenesis in mice by measuring hippocampal PGC-1α mRNA and mitochondrial DNA copy number at 12 and 48 hours. They also tested whether intraperitoneal lactate administration mimicked exercise effects using in vivo microdialysis, examined the role of monocarboxylate transporters using the inhibitor UK5099, and assessed local glycogenolysis by infusing a glycogen phosphorylase inhibitor (1,4-dideoxy-1,4-imino-D-arabinitol) directly into the hippocampus before high-intensity exercise.
What was found
A single bout of high-intensity exercise, but not low- or moderate-intensity exercise, increased hippocampal PGC-1α mRNA and mitochondrial DNA copy number at 12 and 48 hours. Intraperitoneal lactate injection increased hippocampal extracellular lactate to match blood levels and promoted PGC-1α mRNA expression, an effect suppressed by UK5099. UK5099 did not affect running performance or blood lactate after exercise, but it attenuated exercise-induced increases in hippocampal PGC-1α mRNA, mitochondrial DNA copy number, BDNF mRNA, MCT1 mRNA, and MCT2 mRNA (MCT4 was unchanged). Intra-hippocampal glycogen phosphorylase inhibition prevented local glycogen consumption during exercise but did not alter post-exercise hippocampal lactate, PGC-1α, MCT1, or MCT2 mRNA concentrations. The abstract reports no numerical values or effect sizes.
Why it matters
This study delineates a mechanistic link showing that muscle-derived blood lactate produced during high-intensity exercise crosses monocarboxylate transporters into the hippocampus to drive mitochondrial biogenesis and neurotrophic factor expression.
Limits
The study was conducted entirely in mice, limiting generalizability to human brain physiology. The abstract provides no sample sizes, numerical values, or statistical effect estimates. Functional cognitive outcomes and long-term durability beyond 48 hours were not evaluated.
Cited by
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