title: Early-Life Exposure to Lead (Pb) Alters the Expression of microRNA that Target Proteins Associated with Alzheimer's Disease.
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.
authors.affiliation: Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, RI, USA.|Biochemical Technology Program, Faculty of Applied Science, Thamar University, Thamar, Yemen.
authors.forename: Anwar M
authors.initials: AM
authors.lastname: Masoud
authors.affiliation: Department of Pharmacology and Toxicology, College of Pharmacy, University of Hail, Hail, Kingdom of Saudi Arabia.
authors.forename: Syed W
authors.initials: SW
authors.lastname: Bihaqi
authors.affiliation: Lifespan Biostatistics Core and Departments of Orthopaedics and Surgery, Warren Alpert Medical School, Brown University, Providence RI, USA.
authors.forename: Jason T
authors.initials: JT
authors.lastname: Machan
authors.affiliation: Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, RI, USA.|Interdisciplinary Neuroscience Program, University of Rhode Island, Kingston, RI, USA.|George and Anne Ryan Institute for Neuroscience, University of Rhode Island, Kingston, RI, USA.
authors.forename: Nasser H
authors.initials: NH
authors.lastname: Zawia
authors.affiliation: Interdisciplinary Neuroscience Program, University of Rhode Island, Kingston, RI, USA.|George and Anne Ryan Institute for Neuroscience, University of Rhode Island, Kingston, RI, USA.
authors.forename: William E
authors.initials: WE
authors.lastname: Renehan
mesh_terms: D000367:Age Factors; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D007854:Lead / Q000633:toxicity*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D016329:Sp1 Transcription Factor / Q000235:genetics / Q000378:metabolism*
chemical_list: D016564:Amyloid beta-Protein Precursor; D035683:MicroRNAs; D012333:RNA, Messenger; D016329:Sp1 Transcription Factor; D007854:Lead
keywords: Amyloid-β protein precursor; lead; miRNA; neurodegeneration; tau