Circulating insulin-like growth factor I mediates the protective effects of physical exercise against brain insults of different etiology and anatomy.
Physical exercise ameliorates age-related neuronal loss and is currently recommended as a therapeutical aid in several neurodegenerative diseases. However, evidence is still lacking to firmly establish whether exercise constitutes a practical neuroprotective strategy. We now show that exercise provides a remarkable protection against brain insults of different etiology and anatomy. Laboratory rodents were submitted to treadmill running (1 km/d) either before or after neurotoxin insult of the hippocampus (domoic acid) or the brainstem (3-acetylpyridine) or along progression of inherited neurodegeneration affecting the cerebellum (Purkinje cell degeneration). In all cases, animals show recovery of behavioral performance compared with sedentary ones, i.e., intact spatial memory in hippocampal-injured mice, and normal or near to normal motor coordination in brainstem- and cerebellum-damaged animals. Furthermore, exercise blocked neuronal impairment or loss in all types of injuries. Because circulating insulin-like growth factor I (IGF-I), a potent neurotrophic hormone, mediates many of the effects of exercise on the brain, we determined whether neuroprotection by exercise is mediated by IGF-I. Indeed, subcutaneous administration of a blocking anti-IGF-I antibody to exercising animals to inhibit exercise-induced brain uptake of IGF-I abrogates the protective effects of exercise in all types of lesions; antibody-treated animals showed sedentary-like brain damage. These results indicate that exercise prevents and protects from brain damage through increased uptake of circulating IGF-I by the brain. The practice of physical exercise is thus strongly recommended as a preventive measure against neuronal demise. These findings also support the use of IGF-I as a therapeutical aid in brain diseases coursing with either acute or progressive neuronal death.
Carro
E
E
Laboratory of Neuroendocrinology, Cajal Institute, Consejo Superior de Investigaciones Cientificas, 28002 Madrid, Spain.
Trejo
J L
JL
Busiguina
S
S
Torres-Aleman
I
I
D000818:Animals; D001522:Behavior, Animal; D002452:Cell Count; D002526:Cerebellar Diseases / Q000097:blood / Q000473:pathology / Q000628:therapy; D004195:Disease Models, Animal; D018450:Disease Progression; D005947:Glucose / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D007279:Injections, Subcutaneous; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage / Q000378:metabolism*; D007608:Kainic Acid / Q000031:analogs & derivatives*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity; D019636:Neurodegenerative Diseases / Q000209:etiology / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy; D009474:Neurons / Q000473:pathology; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000378:metabolism; D009847:Olivary Nucleus / Q000187:drug effects / Q000473:pathology; D010805:Physical Conditioning, Animal; D011689:Purkinje Cells / Q000473:pathology; D011725:Pyridines; D051381:Rats; D017208:Rats, Wistar; D016896:Treatment Outcome
D018696:Neuroprotective Agents; D011725:Pyridines; C010835:3-acetylpyridine; D007334:Insulin-Like Growth Factor I; D005947:Glucose; C012301:domoic acid; D007608:Kainic Acid