The effects of chronic aluminum exposure on learning and memory of rats by observing the changes of Ras/Raf/ERK signal transduction pathway

Food Chem Toxicol. 2012 Feb;50(2):315-9. doi: 10.1016/j.fct.2011.10.072. Epub 2011 Nov 6.

Abstract

Objective: To investigate the effects of chronic aluminum (Al) exposure on learning and memory function of rats by observing the changes of Ras/Raf/ERK (Ras/ERK) signaling pathway.

Methods: Eighty weaned Wistar rats were divided into four groups ad libitum, 20 rats in each group. The four groups were fed with drinking water containing 0% (control), 0.2%, 0.4% and 0.6% (Al exposure) AlCl(3) for 3months individually to set up aluminum exposure models. The laboratory was maintained at 18-23°C and 45-55% relative humidity. Graphite furnace atomic absorption spectrometry was used to detect the content of Al in brain and blood. Western blot and real-time PCR (RT-PCR) were used to determine the protein and mRNA expression levels for Ras, Raf1, ERK2 and CREB.

Results: Chronic Al exposure increased the content of Al in rats' blood and brain. It increased expression of Ras in the hippocampi compared with the control but the expression decreased along the Al exposure groups (p<0.05). Similarly, Raf1, ERK2 and CREB expressions decreased compared to the control in a dose-dependent manner (p<0.05).

Conclusion: Chronic Al exposure may affect learning and memory through impact on Ras/ERK signal pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aluminum / administration & dosage*
  • Aluminum / toxicity*
  • Animals
  • Cyclic AMP Response Element-Binding Protein / genetics
  • Cyclic AMP Response Element-Binding Protein / metabolism
  • Drug Administration Schedule
  • Gene Expression Regulation / drug effects
  • Learning / drug effects*
  • MAP Kinase Kinase Kinases / genetics
  • MAP Kinase Kinase Kinases / metabolism*
  • MAP Kinase Signaling System / drug effects
  • MAP Kinase Signaling System / physiology
  • Memory / drug effects*
  • Proto-Oncogene Proteins c-raf
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • ras Proteins / genetics
  • ras Proteins / metabolism*

Substances

  • Cyclic AMP Response Element-Binding Protein
  • RNA, Messenger
  • Aluminum
  • Proto-Oncogene Proteins c-raf
  • Raf1 protein, rat
  • MAP Kinase Kinase Kinases
  • ras Proteins