Increased β-amyloid deposition in Tg-SWDI transgenic mouse brain following in vivo lead exposure

Huiying Gu, Gregory Robison, Lan Hong, Raul Barrea, Xing Wei, Martin R. Farlow, Yulia N. Pushkar, Yansheng Du, Wei Zheng

Research output: Contribution to journalArticle

32 Scopus citations

Abstract

Previous studies in humans and animals have suggested a possible association between lead (Pb) exposure and the etiology of Alzheimer's disease (AD). Animals acutely exposed to Pb display an over-expressed amyloid precursor protein (APP) and the ensuing accumulation of beta-amyloid (Aβ) in brain extracellular spaces. This study was designed to examine whether in vivo Pb exposure increased brain concentrations of Aβ, resulting in amyloid plaque deposition in brain tissues. Human Tg-SWDI APP transgenic mice, which genetically over-express amyloid plaques at age of 2-3 months, received oral gavages of 50. mg/kg Pb acetate once daily for 6 weeks; a control group of the same mouse strain received the same molar concentration of Na acetate. ELISA results revealed a significant increase of Aβ in the CSF, brain cortex and hippocampus. Immunohistochemistry displayed a detectable increase of amyloid plaques in brains of Pb-exposed animals. Neurobehavioral test using Morris water maze showed an impaired spatial learning ability in Pb-treated mice, but not in C57BL/6 wild type mice with the same age. In vitro studies further uncovered that Pb facilitated Aβ fibril formation. Moreover, the synchrotron X-ray fluorescent studies demonstrated a high level of Pb present in amyloid plaques in mice exposed to Pb in vivo. Taken together, these data indicate that Pb exposure with ensuing elevated Aβ level in mouse brains appears to be associated with the amyloid plaques formation. Pb apparently facilitates Aβ fibril formation and participates in deposition of amyloid plaques.

Original languageEnglish (US)
Pages (from-to)211-219
Number of pages9
JournalToxicology Letters
Volume213
Issue number2
DOIs
StatePublished - Sep 3 2012

Keywords

  • Amyloid plaques
  • Beta-amyloid or Aβ
  • Fibril formation
  • Hippocampus
  • Lead (Pb)
  • Tg-SWDI mouse
  • X-ray fluorescence or XRF

ASJC Scopus subject areas

  • Toxicology

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