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Characterization of the intergenerational impact of in utero and postnatal oxycodone exposure

Prescription opioid abuse during and after pregnancy is a rising public health concern. While earlier studies have documented that offspring exposed to opioids in utero have impaired neurodevelopment, a significant knowledge gap remains in comparing the overall development between offspring exposed...

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Autores principales: Odegaard, Katherine E., Schaal, Victoria L., Clark, Alexander R., Koul, Sneh, Gowen, Austin, Sankarasubramani, Jagadesan, Xiao, Peng, Guda, Chittibabu, Lisco, Steven J., Yelamanchili, Sowmya V., Pendyala, Gurudutt
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7511347/
https://www.ncbi.nlm.nih.gov/pubmed/32968044
http://dx.doi.org/10.1038/s41398-020-01012-z
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author Odegaard, Katherine E.
Schaal, Victoria L.
Clark, Alexander R.
Koul, Sneh
Gowen, Austin
Sankarasubramani, Jagadesan
Xiao, Peng
Guda, Chittibabu
Lisco, Steven J.
Yelamanchili, Sowmya V.
Pendyala, Gurudutt
author_facet Odegaard, Katherine E.
Schaal, Victoria L.
Clark, Alexander R.
Koul, Sneh
Gowen, Austin
Sankarasubramani, Jagadesan
Xiao, Peng
Guda, Chittibabu
Lisco, Steven J.
Yelamanchili, Sowmya V.
Pendyala, Gurudutt
author_sort Odegaard, Katherine E.
collection PubMed
description Prescription opioid abuse during and after pregnancy is a rising public health concern. While earlier studies have documented that offspring exposed to opioids in utero have impaired neurodevelopment, a significant knowledge gap remains in comparing the overall development between offspring exposed in utero and postnatally. Adding a layer of complexity is the role of heredity in the overall development of these exposed offspring. To fill in these important knowledge gaps, the current study uses a preclinical rat model mimicking oxycodone (oxy) exposure in utero (IUO) and postnatally (PNO) to investigate comparative and intergenerational effects in the two different treatment groups. While significant phenotypic attributes were observed with the two treatments and across the two generations, RNA sequencing revealed alterations in the expression of key synaptic genes in the two exposed groups in both generations. RNA sequencing and post validation of genes using RT-PCR highlighted the differential expression of several neuropeptides associated with the hypocretin system, a system recently implicated in addiction. Further, behavior studies revealed anxiety-like behaviors and social deficits that persisted even in the subsequent generations in the two treatment groups. To summarize, our study for the first time reveals a new line of investigation on the potential risks associated with oxy use during and after pregnancy, specifically the disruption of neurodevelopment and intergenerational impact on behavior.
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spelling pubmed-75113472020-10-08 Characterization of the intergenerational impact of in utero and postnatal oxycodone exposure Odegaard, Katherine E. Schaal, Victoria L. Clark, Alexander R. Koul, Sneh Gowen, Austin Sankarasubramani, Jagadesan Xiao, Peng Guda, Chittibabu Lisco, Steven J. Yelamanchili, Sowmya V. Pendyala, Gurudutt Transl Psychiatry Article Prescription opioid abuse during and after pregnancy is a rising public health concern. While earlier studies have documented that offspring exposed to opioids in utero have impaired neurodevelopment, a significant knowledge gap remains in comparing the overall development between offspring exposed in utero and postnatally. Adding a layer of complexity is the role of heredity in the overall development of these exposed offspring. To fill in these important knowledge gaps, the current study uses a preclinical rat model mimicking oxycodone (oxy) exposure in utero (IUO) and postnatally (PNO) to investigate comparative and intergenerational effects in the two different treatment groups. While significant phenotypic attributes were observed with the two treatments and across the two generations, RNA sequencing revealed alterations in the expression of key synaptic genes in the two exposed groups in both generations. RNA sequencing and post validation of genes using RT-PCR highlighted the differential expression of several neuropeptides associated with the hypocretin system, a system recently implicated in addiction. Further, behavior studies revealed anxiety-like behaviors and social deficits that persisted even in the subsequent generations in the two treatment groups. To summarize, our study for the first time reveals a new line of investigation on the potential risks associated with oxy use during and after pregnancy, specifically the disruption of neurodevelopment and intergenerational impact on behavior. Nature Publishing Group UK 2020-09-23 /pmc/articles/PMC7511347/ /pubmed/32968044 http://dx.doi.org/10.1038/s41398-020-01012-z Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Odegaard, Katherine E.
Schaal, Victoria L.
Clark, Alexander R.
Koul, Sneh
Gowen, Austin
Sankarasubramani, Jagadesan
Xiao, Peng
Guda, Chittibabu
Lisco, Steven J.
Yelamanchili, Sowmya V.
Pendyala, Gurudutt
Characterization of the intergenerational impact of in utero and postnatal oxycodone exposure
title Characterization of the intergenerational impact of in utero and postnatal oxycodone exposure
title_full Characterization of the intergenerational impact of in utero and postnatal oxycodone exposure
title_fullStr Characterization of the intergenerational impact of in utero and postnatal oxycodone exposure
title_full_unstemmed Characterization of the intergenerational impact of in utero and postnatal oxycodone exposure
title_short Characterization of the intergenerational impact of in utero and postnatal oxycodone exposure
title_sort characterization of the intergenerational impact of in utero and postnatal oxycodone exposure
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7511347/
https://www.ncbi.nlm.nih.gov/pubmed/32968044
http://dx.doi.org/10.1038/s41398-020-01012-z
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