Exercise provides an important benefit to overall health and can protect the brain, in particular, from detrimental effects caused by ischemia and oxidative stress. The mechanism of neuroprotection is not well understood, but is hypothesized to involve insulin-like growth factor-1 (IGF-1) and nerve growth factor (NGF). Here, we investigated the ability of forced walking to modulate kainic acid-induced neurotoxicity, and whether IGF-1 plays a role in neuroprotection. Male C57Bl/6J were forced to walk daily for 21 days in a motorized exercise wheel (10 sec/rev., 60 min./day, at 4:00 P.M.) In the evening of day 21, some mice received an injection of either saline or kainic acid (KA, 25 mg/kg, i.p.), providing a total of four treatment groups: saline, kainic acid, exercise + saline, and exercise + kainic acid. Animals were allowed to survive 12 hours and were sacrificed by decapitation. Plasma, brain, liver, and soleus muscle samples were collected for analysis of IGF-1 levels by ELISA (R&D systems kit). Additional animals were processed for histology utilizing the cupric-silver neurodegeneration stain. Chronic exercise did not produce differential levels of IGF-1 in plasma or brain samples, however, plasma levels were approximately 1000 times higher than in brain. Immunohistochemical analysis of exercised animals revealed weak immunoreactivity for IGF-1 in cerebellar Purkinje neurons. Cupric-silver staining revealed an attenuation of KA-induced hippocampal neurotoxicity by exercise pre-conditioning. These data suggest exercise pre conditioning is neuroprotective against excitotoxic injury but that chronic conditioning may involve a multifactorial mechanism incorporating components in addition to growth factors (e.g. increased corticosterone release).
The Toxicologist. Society of Toxicology 45th Annual Meeting and ToxExpo, March 5-9, 2006, San Diego, California