Figure 2.

Physiological response to acute exercise in healthy humans and mice. (A) Transcriptome analysis of peripheral blood mononuclear cells (PMBCs)⁵⁷ reveals that 22% of the biological pathways differentially expressed following acute exercise are significantly enriched with ALS-associated rare genetic variants. The top 30 pathways by P-value are shown. All pathways depicted pass multiple testing correction (FDR < 0.05). (B) The physiological impact of acute exercise in humans measured by gene expression changes in PBMCs. Acute exercise induces an inflammatory response [increasing natural killer (NK) cells, Th1 and Th2 activation, B cell receptors, T cell receptors]. It also increases oxidative stress, apoptosis and upregulates angiogenesis and wound healing pathways [platelet-derived growth factor (PDGF), hepatocyte growth factor (HGF) and epidermal growth factor (EGF)] signalling and dysregulates metabolic pathways, decreasing leptin.⁵⁷ (C) The important gene expression changes in the motor neurons from mice following prolonged regular daily exercise for 6 weeks. Mouse data are depicted as it is not possible to obtain details of the motor neuron transcriptome from living human subjects. The neurotrophic factors and receptors (Cntf, Lifr, Actvr2a) are increased. Genes involved in signalling (Pka1b, Narp, CamkIId) are also increased. Genes involved in ion channels (Kcnd3, Kcne2, Kcnk3) are increased and (Cacng8) is decreased. Genes involved in cytoskeleton reorganization (Arhgap, Gna12, Limk, Acta) are increased, these are involved in neurite outgrowth. P2Y9 and Pctaire, involved in neurite retraction, are decreased.⁵⁸