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https://hdl.handle.net/10356/161457
Title: | Maternal methamphetamine exposure influences behavioral sensitization and nucleus accumbens DNA methylation in subsequent generation | Authors: | Dong, Nan Zhu, Jie Wang, Rui Wang, Shuai Chen, Yanjiong Wang, Changhe Goh, Eyleen Lay Keow Chen, Teng |
Keywords: | Science::Medicine | Issue Date: | 2022 | Source: | Dong, N., Zhu, J., Wang, R., Wang, S., Chen, Y., Wang, C., Goh, E. L. K. & Chen, T. (2022). Maternal methamphetamine exposure influences behavioral sensitization and nucleus accumbens DNA methylation in subsequent generation. Frontiers in Pharmacology, 13, 940798-. https://dx.doi.org/10.3389/fphar.2022.940798 | Project: | MOE2017-T3-1-002 | Journal: | Frontiers in Pharmacology | Abstract: | The deleterious effects of methamphetamine (METH) exposure extend beyond abusers, and may potentially impact the vulnerability of their offspring in developing addictive behaviors. Epigenetic signatures have been implicated in addiction, yet the characteristics to identify prenatal METH abuse to offspring addiction risk remains elusive. Here, we used escalating doses of METH-exposed mouse model in F0 female mice before and during pregnancy to simulate the human pattern of drug abuse and generated METH-induced behavioral sensitization to investigate the addictive behavior in offspring mice. We then utilized whole genome-bisulfite sequencing (WGBS) to investigate the methylation signature of nucleus accumbens (NAc) in male METH-sensitized mice. Interestingly, male but not female offspring exhibited an enhanced response to METH-induced behavioral sensitization. Additionally, the METH-exposed group of male mice underwent a more comprehensive wave of epigenome remodeling over all genomic elements compared with unexposed groups due to drug exposure history. 104,219 DMCs (METH-SAL vs. SAL-SAL) induced by prenatal METH-exposure were positively correlated with that of postnatal METH-exposure (38,570, SAL-METH vs. SAL-SAL). Moreover, 4,983 DMCs induced by pre- and postnatal METH exposure (METH-METH vs. SAL-METH) were negatively correlated with that of postnatal METH exposure, and 371 commonly changed DMCs between the two comparison groups also showed a significantly negative correlation and 86 annotated genes functionally enriched in the pathways of neurodevelopment and addiction. Key annotated genes included Kirrel3, Lrpprc, and Peg3, implicated in neurodevelopmental processes, were down-regulated in METH-METH group mice compared with the SAL-METH group. Taken together, we render novel insights into the epigenetic correlation of drug exposure and provide evidence for epigenetic characteristics that link maternal METH exposure to the intensity of the same drug-induced behavioral sensitization in adult offspring. | URI: | https://hdl.handle.net/10356/161457 | ISSN: | 1663-9812 | DOI: | 10.3389/fphar.2022.940798 | Schools: | Lee Kong Chian School of Medicine (LKCMedicine) | Organisations: | Singhealth Duke-NUS Neuroscience Academic Clinical Programme | Rights: | © 2022 Dong, Zhu, Wang, Wang, Chen, Wang, Goh and Chen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. | Fulltext Permission: | open | Fulltext Availability: | With Fulltext |
Appears in Collections: | LKCMedicine Journal Articles |
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