title: Insulin-like growth factor I interfaces with brain-derived neurotrophic factor-mediated synaptic plasticity to modulate aspects of exercise-induced cognitive function.
abstract: The ability of exercise to benefit neuronal and cognitive plasticity is well recognized. This study reveals that the effects of exercise on brain neuronal and cognitive plasticity are in part modulated by a central source of insulin-like growth factor-I. Exercise selectively increased insulin-like growth factor-I expression without affecting insulin-like growth factor-II expression in the rat hippocampus. To determine the role that insulin-like growth factor-I holds in mediating exercise-induced neuronal and cognitive enhancement, a specific antibody against the insulin-like growth factor-I receptor was used to block the action of insulin-like growth factor-I in the hippocampus during a 5-day voluntary exercise period. A two-trial-per-day Morris water maze was performed for five consecutive days, succeeded by a probe trial 2 days later. Blocking hippocampal insulin-like growth factor-I receptors did not significantly attenuate the ability of exercise to enhance learning acquisition, but abolished the effect of exercise on augmenting recall. Blocking the insulin-like growth factor-I receptor significantly reversed the exercise-induced increase in the levels of brain-derived neurotrophic factor mRNA and protein and pro-brain-derived neurotrophic factor protein, suggesting that the effects of insulin-like growth factor-I may be partially accomplished by modulating the precursor to the mature brain-derived neurotrophic factor. A molecular analysis revealed that exercise significantly elevated proteins downstream to brain-derived neurotrophic factor activation important for synaptic function, i.e. synapsin I, and signal transduction cascades associated with memory processes, i.e. phosphorylated calcium/calmodulin protein kinase II and phosphorylated mitogen-activated protein kinase II. Blocking the insulin-like growth factor-I receptor abolished these exercise-induced increases. Our results illustrate a possible mechanism by which insulin-like growth factor-I interfaces with the brain-derived neurotrophic factor system to mediate exercise-induced synaptic and cognitive plasticity.
authors.affiliation: Department of Physiological Science, UCLA, 621 Charles E. Young Drive, Los Angeles, CA 90095, USA.
authors.forename: Q
authors.initials: Q
authors.lastname: Ding
authors.forename: S
authors.initials: S
authors.lastname: Vaynman
authors.forename: M
authors.initials: M
authors.lastname: Akhavan
authors.forename: Z
authors.initials: Z
authors.lastname: Ying
authors.forename: F
authors.initials: F
authors.lastname: Gomez-Pinilla
mesh_terms: D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D003071:Cognition / Q000187:drug effects / Q000502:physiology*; D005081:Exercise Therapy; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000502:physiology; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008568:Memory / Q000187:drug effects / Q000502:physiology; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D010805:Physical Conditioning, Animal / Q000502:physiology*; D011498:Protein Precursors / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017526:Receptor, IGF Type 1 / Q000276:immunology / Q000378:metabolism; D016704:Synapsins / Q000378:metabolism; D009435:Synaptic Transmission / Q000502:physiology; D015854:Up-Regulation / Q000502:physiology
chemical_list: D000906:Antibodies; D019208:Brain-Derived Neurotrophic Factor; D011498:Protein Precursors; D012333:RNA, Messenger; D016704:Synapsins; C426674:brain-derived neurotrophic factor precursor; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases