Exercise Provides Neuroprotection Against Kainic Acid Toxicity Through Induction of the Chemokine Mcp-1 in the Hippocampus of C57BL/6J Mice

Details

• Personal Author:
  Benkovic SA ; Miller DB ; O'Callaghan JP ; Sriram K
• Description:
  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. [Description provided by NIOSH]
• Subjects:
  Animals Chemistry Nervous System Occupational Health Risk Assessment Risk Factors Safety Workplace
• Keywords:
  Animal-studies Cell-biology Cell-damage Cellular-reactions Chemical-analysis Chemical-reactions Dose-response Excretion Nervous-system-function Neurological-reactions Physical-exercise Physical-reactions Physiological-chemistry Physiological-effects Physiological-response Physiological-testing Risk-analysis Risk-factors Work-environment

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• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  OSHA Region 3 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  96
• Issue:
  1
• NIOSHTIC Number:
  nn:20031931
• Citation:
  Toxicologist 2007 Mar; 96(1):309
• Federal Fiscal Year:
  2007
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 46th Annual Meeting and ToxExpo, March 25-29, 2007, Charlotte, North Carolina
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:8af01b81426dfcd247e87082a6fefece285283159318d845733fdafceb6c6fed32a4903f286fedc292a5cf2a921bcf4cc91bde930136776a3cc165631c96979d
• Download URL:
  https://stacks.cdc.gov/view/cdc/186041/cdc_186041_DS1.pdf
• File Type:
  [PDF - 523.67 KB ]