EPA Science Inventory

AIR POLLUTION, OXIDATIVE STRESS AND NEUROTOXICITY.

Citation:

CAMPBELL, A., S. M. MOHANKUMAR, AND B. VERONESI. AIR POLLUTION, OXIDATIVE STRESS AND NEUROTOXICITY. Presented at International Neurotoxicology Association, San Antonio, TX, November 11 - 14, 2007.

Description:

Increased incidents of classic and variant forms of neurodegenerative diseases suggest that environmental chemicals and susceptibility factors (e.g., genetics, diseased states, obesity, etc.) may be contributory. Particulate matter (PM) is a type of air pollution that is associated with sudden deaths in the elderly and respiratory distress in susceptible populations (e.g., asthmatics). PM particles contain numerous biological (e.g., bacterial) and chemical (e.g., pesticides, transition metals) contaminants on their surface that convey free radical activity and damage target cells and tissues through oxidative stress (OS) pathways. Although toxicity studies have largely focused on PM’s cardiopulmonary targets, recent reports indicate that nanosize PM particles exit the lungs shortly after inhalation, enter the systemic circulation and distribute to numerous organ systems, including the brain. Since the brain is highly vulnerable to OS-damage, its neurotoxic susceptibility to PM exposure was examined. This poster will highlight the results of three independent studies that link PM, OS and neurotoxicity (neurochemical, neuropathological) using normal (C57) and transgenic (ApoE -/-) mice exposed by inhalation to concentrated ambient PM (CAPs). Data generated from these studies confirm that PM stimulates inflammatory changes in the brain along innate immunity pathways, alters neurotransmitter levels that are key to the neurodocrine stress response, and produces neurodegeneration in the OS-sensitive neurons of the substantia nigra of exposed mice. In vitro studies of immortalized microglia exposed to CAPs indicate that they respond with cellular and genomic endpoints indicating an up-regulation of OS pathways and Toll-like receptors. Together these data-sets confirm that the brain is targeted by PM air pollution and that OS is an important predisposing factor to this susceptibility. (This abstract has been reviewed by the USEPA, NHEERL and does not necessarily reflect Agency policy).

Purpose/Objective:

This poster will highlight the results of three independent studies that link PM, OS and neurotoxicity (neurochemical, neuropathological) using normal (C57) and transgenic (ApoE -/-) mice exposed by inhalation to concentrated ambient PM (CAPs).

URLs/Downloads:

Record Details:

Record Type: DOCUMENT (PRESENTATION/ABSTRACT)
Start Date: 11/12/2007
Completion Date: 11/12/2007
Record Last Revised: 05/07/2008
Record Created: 10/10/2007
Record Released: 10/10/2007
OMB Category: Other
Record ID: 185609

Organization:

U.S. ENVIRONMENTAL PROTECTION AGENCY

OFFICE OF RESEARCH AND DEVELOPMENT

NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LAB

NEUROTOXICOLOGY DIVISION

CELLULAR AND MOLECULAR TOXICOLOGY BRANCH