Increased ß-amyloid deposition in Tg-SWDI transgenic mouse brain following in vivo lead exposure.
Toxicol Lett
; 213(2): 211-9, 2012 Sep 03.
Article
en En
| MEDLINE
| ID: mdl-22796588
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 (Aß) in brain extracellular spaces. This study was designed to examine whether in vivo Pb exposure increased brain concentrations of Aß, 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 Aß 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 Aß 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 Aß level in mouse brains appears to be associated with the amyloid plaques formation. Pb apparently facilitates Aß fibril formation and participates in deposition of amyloid plaques.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Encéfalo
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Péptidos beta-Amiloides
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Enfermedad de Alzheimer
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Plomo
Límite:
Animals
Idioma:
En
Revista:
Toxicol Lett
Año:
2012
Tipo del documento:
Article
País de afiliación:
Estados Unidos