Affiliations: [a] Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, RI, USA | [b] Biochemical Technology Program, Faculty of Applied Science, Thamar University, Thamar, Yemen | [c] Department of Pharmacology and Toxicology, College of Pharmacy, University of Hail, Hail, Kingdom of Saudi Arabia | [d] Lifespan Biostatistics Core and Departments of Orthopaedics and Surgery, Warren Alpert Medical School, Brown University, Providence RI, USA | [e] Interdisciplinary Neuroscience Program, University of Rhode Island, Kingston, RI, USA | [f] George and Anne Ryan Institute for Neuroscience, University of Rhode Island, Kingston, RI, USA
Correspondence:
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Correspondence to: William E. Renehan, PhD, Director of Research, College of Pharmacy, Associate Director of George and Anne Ryan Institute for Neuroscience, University of Rhode Island, 7 Greenhouse Road, Kingston, RI 02881, USA. Tel.: +1 401 874 9304; Fax: +1 401 874 2181; E-mail: [email protected].
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.
Keywords: Amyloid-β protein precursor, lead, miRNA, neurodegeneration, tau
