Neurotoxic Doses of Chronic Methamphetamine  Trigger Retrotransposition of the Identifier Element  in Rat Dorsal Dentate Gyrus

Short interspersed elements (SINEs) are typically silenced by DNA hypermethylation in somatic cells, but can retrotranspose in proliferating cells during adult neurogenesis. Hypomethylation caused by disease pathology or genotoxic stress leads to genomic instability of SINEs. The goal of the present...

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Bibliographic Details
Published in:Genes 2017-03, Vol.8 (3), p.96
Main Authors: Moszczynska, Anna, Burghardt, Kyle J, Yu, Dongyue
Format: Article
Language:English
Subjects:
Coding
CpG islands
Dentate gyrus
Deoxyribonucleic acid
DNA
DNA methylation
DNA sequencing
Genomic instability
Genotoxicity
Hippocampus
Immunohistochemistry
Methamphetamine
Neurogenesis
Neurotoxicity
Poly(A)
Proteins
Retrotransposition
Somatic cells
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Summary:Short interspersed elements (SINEs) are typically silenced by DNA hypermethylation in somatic cells, but can retrotranspose in proliferating cells during adult neurogenesis. Hypomethylation caused by disease pathology or genotoxic stress leads to genomic instability of SINEs. The goal of the present investigation was to determine whether neurotoxic doses of binge or chronic methamphetamine (METH) trigger retrotransposition of the identifier (ID) element, a member of the rat SINE family, in the dentate gyrus genomic DNA. Adult male Sprague-Dawley rats were treated with saline or high doses of binge or chronic METH and sacrificed at three different time points thereafter. DNA methylation analysis, immunohistochemistry and next-generation sequencing (NGS) were performed on the dorsal dentate gyrus samples. Binge METH triggered hypomethylation, while chronic METH triggered hypermethylation of the CpG-2 site. Both METH regimens were associated with increased intensities in poly(A)-binding protein 1 (PABP1, a SINE regulatory protein)-like immunohistochemical staining in the dentate gyrus. The amplification of several ID element sequences was significantly higher in the chronic METH group than in the control group a week after METH, and they mapped to genes coding for proteins regulating cell growth and proliferation, transcription, protein function as well as for a variety of transporters. The results suggest that chronic METH induces ID element retrotransposition in the dorsal dentate gyrus and may affect hippocampal neurogenesis.
ISSN:2073-4425
2073-4425
DOI:10.3390/genes8030096