Peripheral to brain and hippocampus crosstalk induced by exercise mediates cognitive and structural hippocampal adaptations

Endurance exercise leads to robust increases in memory and learning. Several exercise adaptations occur to mediate these improvements, including in both the hippocampus and in peripheral organs. Organ crosstalk has been becoming increasingly more present in exercise biology, and studies have shown that peripheral organs can communicate to the hippocampus and mediate hippocampal changes. Both learning and memory as well as other hippocampal functional-related changes such as neurogenesis, cell proliferation, dendrite morphology and synaptic plasticity are controlled by these exercise responsive peripheral proteins. These peripheral factors, also called exerkines, are produced by several organs including skeletal muscle, liver, adipose tissue, kidneys, adrenal glands and circulatory cells. Previous reviews have explored some of these exerkines including muscle-derived irisin and cathepsin B (CTSB), but a full picture of peripheral to hippocampus crosstalk with novel exerkines such as selenoprotein 1 (SEPP1) and platelet factor 4 (PF4), or old overlooked ones such as lactate and insulin-like growth factor 1 (IGF-1) is still missing. We provide 29 different studies of 14 different exerkines that crosstalk with the hippocampus. Thus, the purpose of this review is to explore peripheral exerkines that have shown to exert hippocampal function following exercise, demonstrating their particular effects and molecular mechanisms in which they could be inducing adaptations.