Interoceptive Signaling by Circulating Insulin Like Growth Factor I and Neuroprotection by Exercise.

Physical activity has been proven to be beneficial for brain function. Due to a lack of appropriate therapies for the majority of brain diseases, exercise has become a favored alternative to prevent and even treat several of these pathologies. Thus, the mechanisms underlying the neuroprotective actions of exercise are under intense scrutiny. Furthermore, since many patients afflicted with different neurological conditions are not able to perform exercise, development of pharmacological mimics based on knowledge of underlying cellular and molecular mechanisms is of therapeutic interest (Narkar VA, Downes M, Yu RT, Embler E, Wang YX, Banayo E, Cell 134:405-415, 2008). As part of these mechanisms, we will examine the role of insulin-like growth factor I (IGF-I), a pleiotropic neuroprotective signal, and one of the established mediators of the beneficial actions of exercise in the brain. Exercise stimulates the entrance of circulating IGF-I into the brain where it mediates pro-neurogenic, pro-cognitive, and mood modulatory effects known to be associated to exercise. Through its potent cytoprotective actions (anti-apoptotic, anti-oxidant, anti-inflammatory), IGF-I participates in reparative and homeostatic processes associated to exercise. We postulate that circulating IGF-I, a regulator of muscle and bone mass, forms part of an interoceptive system within a humoral branch informing the brain of muscle/bone mass. In this way, IGF-I conveys interoceptive signaling to brain areas involved in orchestrating physical activity to adapt them to available vigor, i.e., muscle strength. Because exercise engages the activity of many brain areas, neuroprotection by exercise-elicited entrance of circulating IGF-I is brain-wide.