Title | Early-Life Exposure to Lead (Pb) Alters the Expression of microRNA that Target Proteins Associated with Alzheimer's Disease. |
Publication Type | Journal Article |
Year of Publication | 2016 |
Authors | Masoud, AM, Bihaqi, SW, Machan, JT, Zawia, NH, Renehan, WE |
Journal | J Alzheimers Dis |
Volume | 51 |
Issue | 4 |
Pagination | 1257-64 |
Date Published | 2016 |
ISSN | 1875-8908 |
Keywords | Age Factors, Amyloid beta-Protein Precursor, Animals, Animals, Newborn, Disease Models, Animal, Dose-Response Relationship, Drug, Female, Gene Expression Regulation, Developmental, Lead, Male, Mice, Mice, Inbred C57BL, MicroRNAs, Pregnancy, RNA, Messenger, Sp1 Transcription Factor |
Abstract | There is a growing recognition of the impact of environmental toxins on the epigenetic regulation of gene expression, including the genes that play a critical role in neural development, neural function, and neurodegeneration. We have shown previously that exposure to the heavy metal lead (Pb) in early life results in a latent over-expression of AD-related proteins in rodents and primates. The present study provides evidence that early postnatal exposure to Pb also alters the expression of select miRNA. Mice were exposed to 0.2% Pb acetate from Postnatal Day 1 (PND 1, first 24 h after birth) to PND 20 via their mother's milk. Brain tissue was harvested at PND 20, 180, or 700, and miRNA were isolated and quantified by qPCR. This exposure produced a transient increase (relative to control) in the expression of miR-106b (binds to AβPP mRNA), miR-29b (targets the mRNA for the transcription factor SP1) and two miRNAs (miR-29b and miR-132) that have the ability to inhibit translation of proteins involved in promoter methylation. The expression of miR-106b decreased over time in the Pb-exposed animals and was significantly less than the levels exhibited by the control animals at PND700. The level of miR-124, which binds to SP1 mRNA, was also reduced (relative to controls) at PND700. In summary, we show that exposure to the heavy metal Pb in early life has a significant impact on the short- and long-term expression of miRNA that target epigenetic mediators and neurotoxic proteins. |
DOI | 10.3233/JAD-151018 |
Alternate Journal | J. Alzheimers Dis. |
PubMed ID | 26923026 |
Grant List | ES015867 / ES / NIEHS NIH HHS / United States P20RR016457 / RR / NCRR NIH HHS / United States |
- Comment
|