Physical exercise affords protection to neurons exposed to the excitotoxicant kainic acid (KA). We previously observed attenuation in KA-induced argyrophilia and blood-brain barrier disruption following a 14-day regimen of forced walking in male C57BL/6J mice. Here, we investigated the role of microglial activation in the hippocampus, and the production of microglial-derived factors in the protective mechanism. Mice were assigned randomly to one of four experimental groups: saline, kainic acid, exercise + saline, exercise + KA. Forced walking was achieved in a motorized exercise wheel (6 rpm, 60 min duration, 4:00 PM daily). Mice were acclimated to the wheels for three days, exercised for 14 days, and given an intraperitoneal injection of KA (25 mg/kg). Control animals were not exercised, and received a comparable injection of saline. Following a 12-hour survival, animals were sacrificed and their brains were dissected into regions for RNA extraction and analysis of microglial markers and secretory products by RT-PCR. KA treatment caused a four-fold induction in hippocampal levels of the neurotrophic factor Gdnf, and a two-fold induction in Igf-1: bdnf levels were slightly but non-significantly elevated. Microglial markers, F4/80, Iba1, Mac-1, and p67Phox were unchanged between experimental groups. KA treatment caused a 3-fold induction in Il-1alpha and Il-6 levels, a 15-fold induction in Tnf-alpha levels, and an 8-fold induction in Mcp-1 that was increased to 23-fold by exercise pretreatment. Our data suggest the protective effects of exercise against excitotoxicity may occur through modulation of the neuroinflammatory response, and may be mediated through the chemokine Mcp-1. Subsequent experimentation will evaluate the protective effects of exercise in Mcp-1 knockout mice.
Physical-reactions; Risk-analysis; Risk-factors; Dose-response; Chemical-analysis; Chemical-reactions; Work-environment; Animal-studies; Cell-biology; Cell-damage; Cellular-reactions; Excretion; Physical-exercise; Physical-reactions; Physiological-response; Physiological-chemistry; Physiological-effects; Physiological-testing; Nervous-system-function; Neurological-reactions
The Toxicologist. Society of Toxicology 46th Annual Meeting and ToxExpo, March 25-29, 2007, Charlotte, North Carolina