Lactate and BDNF: Key Mediators of Exercise Induced Neuroplasticity?

Abstract

Accumulating evidence from animal and human studies supports the notion that physical exercise can enhance neuroplasticity and thus reduce the risk of several neurodegenerative diseases (e.g., dementia). However, the underlying neurobiological mechanisms of exercise induced neuroplasticity are still largely unknown. One potential mediator of exercise effects is the neurotrophin BDNF, which enhances neuroplasticity via different pathways (e.g., synaptogenesis, neurogenesis, long-term potentiation). Current research has shown that (i) increased peripheral lactate levels (following high intensity exercise) are associated with increased peripheral BDNF levels, (ii) lactate infusion at rest can increase peripheral and central BDNF levels and (iii) lactate plays a very complex role in the brain's metabolism. In this review, we summarize the role and relationship of lactate and BDNF in exercise induced neuroplasticity.

Keywords: BDNF; lactate; neuroplasticity; physical exercise.

Figure 1

Potential mechanisms of lactate-BDNF interaction following physical exercise. Physical exercise is associated with intensity-dependent increase of lactate levels. Lactate can cross the blood-brain barrier (BBB) via different monocarboxylate transporters (MCT‘s). Furthermore, lactate binding to the hydroxycarboxylic acid receptor (HCAR1) at the BBB can induce angiogenesis. In neurons, lactate exerts several neurotrophic and metabolic effects through transmembrane transport via MCT’s and direct binding to HCAR1. Firstly, lactate binding to HCAR1 on neurons inhibits the adenylate cyclase (AC) and thus decreases cAMP, resulting reduced BDNF expression and regulatory function in the control of blood flow, and synaptic functions. Secondly, lactate can induce the PGC1α/FNDC5/BDNF pathway through SIRT1 activation. Thirdly, lactate increases intracellular NADH, resulting in enhanced calcium levels and BDNF gene expression. Released BDNF can then enhance neuroplasticity via different neurobiological mechanisms (e.g., neurogenesis, synaptogenesis, growth of dendritic spines, long-term potentiation [LTP]).