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ORIGINAL RESEARCH article

Front. Cell. Neurosci.

Sec. Cellular Neuropathology

Volume 19 - 2025 | doi: 10.3389/fncel.2025.1644843

This article is part of the Research TopicMechanisms of exercise-induced changes in amyloid precursor protein processingView all articles

Lactate Infusion Increases Circulating pro-Brain-Derived Neurotrophic Factor Levels in Humans

Provisionally accepted
Julia  RöjaJulia Röja1Nicolas  Fiori AmellerNicolas Fiori Ameller1Jonathan  GripJonathan Grip2William  ApróWilliam Apró1,2Marcus  MobergMarcus Moberg1,3*
  • 1Department of Physiology, Nutrition and Biomechanics, Swedish School of Sport and Health Sciences, Stockholm, Sweden
  • 2Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden
  • 3Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden

The final, formatted version of the article will be published soon.

Brain-derived neurotrophic factor (BDNF) is a key mediator of neuroplasticity and responsive to acute physical exercise, providing a link between exercise and brain health. Lactate, a metabolite related to exercise, has been proposed as a potential mediator of the BDNF exercise response; however, lactate's role in isolation has not yet been determined. To investigate this, 18 young, healthy volunteers (50 % female) were recruited to donate blood and muscle before, during, and after a one-hour venous infusion of sodium lactate (125 µmol × kg FFM-1 × min-1) or isotonic saline. Muscle and blood samples were collected during 120 min of recovery from the infusion. Samples were analyzed for pro-BDNF and mBDNF using enzyme-linked immunosorbent assay and immunoblotting. The participants reached a peak plasma lactate level of 5.9  0.37 mmol × L-1 in the lactate trial (p = 0.0002 vs. Pre). Plasma pro-BDNF levels increased 15 min post lactate infusion and stayed elevated throughout the recovery (55-68 %, p < 0.0286 vs. Saline) while plasma and serum levels of mBDNF showed no significant change (p > 0.05 vs. Saline). Muscle pro-BDNF levels were also unaltered by the lactate infusion (p > 0.05 vs. Saline); however, the expression of pro-BDNF correlated with the proportion of type I muscle fiber area (fCSA%) of the participants (n = 18, r = 0.6746, p = 0.0021). Muscle levels of the mBDNF isoform were non-detectable. In conclusion, these results suggest that lactate in isolation affects circulatory pro-BDNF, but not mBDNF levels. This implies that lactate may partly mediate the exercise response of pro-BDNF in humans.

Keywords: BDNF, pro-BDNF, Lactate infusion, human, skeletal muscle, cortisol, BDNF polymorphism, Fiber type

Received: 10 Jun 2025; Accepted: 29 Jul 2025.

Copyright: © 2025 Röja, Fiori Ameller, Grip, Apró and Moberg. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Marcus Moberg, Department of Physiology, Nutrition and Biomechanics, Swedish School of Sport and Health Sciences, Stockholm, Sweden

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