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Neurotoxicology. 2014 Sep;44:114-20. doi: 10.1016/j.neuro.2014.06.008. Epub 2014 Jun 20.

Infantile postnatal exposure to lead (Pb) enhances tau expression in the cerebral cortex of aged mice: relevance to AD.

Author information

1
Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, RI, USA.
2
Department of Pharmacology, College of Medicine, United Arab Emirates University, Al-Ain, United Arab Emirates.
3
Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, RI, USA; Interdisciplinary Neuroscience Program (INP), University of Rhode Island, Kingston, RI, USA. Electronic address: nzawia@uri.edu.

Abstract

The sporadic nature in over 90% of Alzheimer's disease (AD) cases, the differential susceptibility and course of illness, and latent onset of the disease suggest involvement of an environmental component in the etiology of late onset AD (LOAD). Recent reports from our lab have demonstrated that molecular alterations favor abundant tau phosphorylation and immunoreactivity in the frontal cortex of aged primates with infantile lead (Pb) exposure (Bihaqi and Zawia, 2013). Here we report that developmental Pb exposure results in elevation of protein and mRNA levels of tau in aged mice. Western blot analysis revealed aberrant site-specific tau hyperphosphorylation accompanied by elevated cyclin dependent kinase 5 (CDK5) levels in aged mice with prior Pb exposure. Mice with developmental Pb exposure also displayed altered protein ratio of p35/p25 with more Serine/Threonine phosphatase activity at old age. These changes favored increase in tau phosphorylation, thus providing evidence that neurodegenerative diseases may be in part due to environmental influences that occur during development.

KEYWORDS:

Aging; CDK5; Hyperphosphorylation; Lead; Tau

PMID:
24954411
PMCID:
PMC4175119
DOI:
10.1016/j.neuro.2014.06.008
[Indexed for MEDLINE]
Free PMC Article
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