. Exercise Induces Hippocampal BDNF through a PGC-1α/FNDC5 Pathway. Cell Metab. 2013 Oct 8; PubMed.


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  1. Numerous studies going back to the 1990s provided evidence that physical exercise raises BDNF mRNA and protein levels in the mammalian brain. Partly as a consequence of these (mostly) animal studies, “physical mobilization” is a now a more commonly tested intervention to improve cognitive as well as memory performance of elderly people at risk of dementia. Nonetheless, molecular mechanisms to explain how skeletal muscle activity eventually led to raised BDNF levels, which are most likely responsible for this cognitive stabilization, remained elusive.

    This paper by Wrann et al. now provides the first insight into molecular messengers that are likely to be involved. The cleavage product of the muscle protein FNDC5—irisin—is released into the bloodstream by active muscles during exercise. It seems to be able to cross the blood-brain barrier and increase BDNF expression in brain areas important for memory formation.

    Numerous exciting questions arise, for example: Can irisin also influence the neuronal secretion of BDNF, which would be needed in the extracellular space to induce better memory formation?
    Can synthetized irisin—exogenously provided to the blood stream—increase BDNF levels and thus induce better cognitive performance, hinting at a possible future therapy for dementia? If neurons can express FNDC5 themselves, why do they need muscle FNDC5-derived irisin to increase their BDNF levels?

    This paper is exciting and seems to be a first step toward understanding why exercise is advantageous not only for physical but also mental health.

    View all comments by Volkmar Lessmann

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