Chronic Exposure to Low Levels of Aluminum Alters Cerebral Cell Signaling in Response to Acute MPTP Administration

Details

• Personal Author:
  Ali SF ; Bondy SC ; Campbell A ; Cong P ; Li H
• Description:
  Two-month-old male B/6C3F1 mice were treated for 10 weeks with 100 uM aluminum lactate (Al) in drinking water. This dose of Al did not alter body weight, and there was no evidence of systemic toxicity. The degree of phosphorylation of several kinases which lead to transcription factor activation (reflecting the extent of their activation) was studied. The proportion of extracellular signal-regulated kinase (ERK) that was activated was depressed in cortex but not in the hippocampus following treatment but c-Jun N-terminal kinase (JNK), p38, IkB phosphorylation was unaltered in either tissue. Treatment of mice with 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP) alone produced no significant changes in the degree of activation of any transcription factor studied. When MPTP dosing had been preceded by extended exposure to low levels of Al in drinking water, ERK activation was profoundly depressed in cortex and hippocampus, whereas JNK in hippocampus and IkB in cortex were greatly elevated. These changes consequent to exposure to both Al and MPTP were accompanied by an increase in NF-kB in both regions, whereas AP-1 was elevated in the hippocampus alone. Neither agent alone modulated AP-1 or NF-kB. Thus a synergistic interaction occurred between the toxicants. This interaction tended to promote the functioning of a kinase largely associated with inflammation and to depress that of ERK, which is associated with maintenance of cell survival. It is concluded that exposure to levels of Al with no evident toxicity can worsen the response to an acute challenge with MPTP. Al treatment alone was able to increase striatal 3,4-dihydroxyphenylacetic acid levels, suggesting an elevation of the rate of dopamine turnover in the striatum. However, no interaction in alteration of monoamine levels was found between Al and MPTP. [Description provided by NIOSH]
• Subjects:
  Aluminum Compounds Animals Occupational Exposure Occupational Health Safety Toxicology
• Keywords:
  Aluminum Animal Studies Author Keywords: Aluminum Brain Function Cell Signaling Cellular Effects Chronic Exposure Inflammation MPTP
• ISSN:
  0748-2337
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  Arkansas ; California ; OSHA Region 6 ; OSHA Region 9
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  23
• Issue:
  9
• NIOSHTIC Number:
  nn:20058485
• Citation:
  Toxicol Ind Health 2007 Oct; 23(9):515-524
• Contact Point Address:
  Stephen C Bondy, PhD, Department of Community and Environmental Medicine, University of California, Irvine, CA 92697-1825, USA
• Email:
  scbondy@uci.edu
• CAS Registry Number:
  Aluminum (CAS RN 7429-90-5)
• Federal Fiscal Year:
  2008
• Performing Organization:
  University of California Los Angeles
• Peer Reviewed:
  True
• Start Date:
  20050701
• Source Full Name:
  Toxicology and Industrial Health
• End Date:
  20270630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:48af0d00723cbe80f92e2c24ca9cc46858d7b796ea75fd3afdf6598739d2af5805093087bb8de93c1f9f5a09fd2d95501328f7855cae684bf30241f19bfe0a47
• Download URL:
  https://stacks.cdc.gov/view/cdc/221572/cdc_221572_DS1.pdf
• File Type:
  [PDF - 901.81 KB ]