Skip directly to search Skip directly to A to Z list Skip directly to page options Skip directly to site content

NIOSHTIC-2 Publications Search

Search Results

Exercise provides neuroprotection against kainic acid toxicity through induction of the chemokine mcp-1 in the hippocampus of C57BL/6J mice.

Benkovic-SA; Sriram-K; O'Callaghan-JP; Miller-DB
Toxicologist 2007 Mar; 96(1):309
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
Publication Date
Document Type
Fiscal Year
NTIS Accession No.
NTIS Price
Issue of Publication
NIOSH Division
Source Name
The Toxicologist. Society of Toxicology 46th Annual Meeting and ToxExpo, March 25-29, 2007, Charlotte, North Carolina