Aluminum Disrupts the Pro-Inflammatory Cytokine/Neurotrophin Balance in Primary Brain Rotation-Mediated Aggregate Cultures: Possible Role in Neurodegeneration

Details

• Personal Author:
  Johnson VJ ; Sharma RP
• Description:
  The etiology of human neurodegenerative diseases including Alzheimer's disease (AD) is exceedingly complex and our understanding of the mechanisms involved is far from complete. The experimental neurotoxicology of aluminum has been shown to recapitulate many of the pathophysiological features of AD and therefore represents a useful model to study the mechanisms involved in neurodegeneration. The present study investigated the effects of aluminum maltolate (Al-maltol) on the delicate balance that exists between pro-inflammatory cytokines and neurotrophins using primary brain rotation-mediated aggregate cultures. Aggregates were treated with Al-maltol (50-150 M) on day 15 in vitro for 72 h. Cell death increased in a time- and concentration-dependent manner reaching significance in aggregates treated with 150 M Al-maltol in 48 h and 50 M by 72 h. Analysis of gene expression at 72 h revealed a concentration-dependent increase in tumor necrosis factor alpha (TNF) and macrophage inflammatory protein-1alpha (MIP-1alpha) suggestive of a state of inflammation. In contrast, a dramatic concentration-dependent decrease in the expression of nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF) was observed. In fact, NGF expression could not be detected in aggregates treated with 50 and 150 M Al-maltol. These changes in gene expression correlated with a decrease in aggregate size and an increase in neurodegeneration as indicated by Fluoro-Jade B staining. The results indicated a differential regulation of pro-inflammatory cytokines and neurotrophins in brain tissue following treatment with Al-maltol. Such findings provide insight into the possible involvement of deregulation of the cytokine/neurotrophin balance in the etiology of neurodegeneration. [Description provided by NIOSH]
• Subjects:
  Aluminum Compounds Cytotoxins Nervous System Nervous System Diseases Occupational Health Safety
• Keywords:
  Aluminum-compounds Analytical-methods Analytical-models Cytotoxic-effects Neurological-diseases Neurological-system Pathogens Physiological-disorders Physiological-function Statistical-analysis
• ISSN:
  0161-813X
• Document Type:
  Text
• Genre:
  Journal Article
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  261-268
• Volume:
  24
• Issue:
  2
• NIOSHTIC Number:
  nn:20027621
• Citation:
  Neurotoxicology 2003 Mar; 24(2):261-268
• CAS Registry Number:
  Aluminum (CAS RN 7429-90-5) ; Tris[3-(hydroxy-κO)-2-methyl-4H-pyran-4-onato-κO4]aluminum (CAS RN 23058-19-7)
• Federal Fiscal Year:
  2003
• Peer Reviewed:
  True
• Source Full Name:
  Neurotoxicology
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:a857276f21380e3aabc67d0cf4d2a3de6ff0d8303609fe227fdf537ccb9f9db92df34de79f386d61a46eef5e8e10fa8f3bdeba3f2ce65b4575131546d3fcdc28
• Download URL:
  https://stacks.cdc.gov/view/cdc/197606/cdc_197606_DS1.pdf
• File Type:
  [PDF - 324.94 KB ]