Increased β-amyloid deposition in Tg-SWDI transgenic mouse brain following in vivo lead exposure.
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 50mg/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.
Department of Neurology, School of Medicine, Indiana University, Indianapolis, IN 46202, United States. huiygu@iupui.edu
Huiying
H
Gu
Gregory
G
Robison
Lan
L
Hong
Raul
R
Barrea
Xing
X
Wei
Martin R
MR
Farlow
Yulia N
YN
Pushkar
Yansheng
Y
Du
Wei
W
Zheng
D000544:Alzheimer Disease / Q000139:chemically induced* / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D007854:Lead / Q000134:cerebrospinal fluid / Q000633:toxicity*; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D058225:Plaque, Amyloid / Q000139:chemically induced / Q000737:chemistry / Q000378:metabolism; D013052:Spectrometry, X-Ray Emission
D016229:Amyloid beta-Peptides; D007854:Lead