A Holistic Systems Approach to Characterize the Impact of Pre- and Post-natal Oxycodone Exposure on Neurodevelopment and Behavior

Authors

Katherine E. Odegaard, University of Nebraska Medical CenterFollow
Victoria L. Schaal, University of Nebraska Medical CenterFollow
Alexander R. Clark, University of Nebraska Medical Center
Sneh Koul, University of Nebraska Medical Center
Jagadesan Sankarasubramanian, University of Nebraska Medical CenterFollow
Zhiqiu Xia, University of Nebraska Medical CenterFollow
Melissa Mellon, University of Nebraska Medical CenterFollow
Mariano Uberti, University of Nebraska Medical CenterFollow
Yutong Liu, University of Nebraska Medical CenterFollow
Andrew Stothert, University of Nebraska Medical CenterFollow
Matthew J. Van Hook, University of Nebraska Medical CenterFollow
Han-Jun Wang, University of Nebraska Medical CenterFollow
Chittibabu Guda, University of Nebraska Medical CenterFollow
Steven J. Lisco, University of Nebraska Medical CenterFollow
Gurudutt Pendyala, University of Nebraska Medical Center, OmahaFollow
Sowmya V. Yelamanchili, University of Nebraska Medical CenterFollow

Document Type

Article

Journal Title

Frontiers in Cell and Developmental Biology

Publication Date

2021

Volume

8

Abstract

Background: Increased risk of oxycodone (oxy) dependency during pregnancy has been associated with altered behaviors and cognitive deficits in exposed offspring. However, a significant knowledge gap remains regarding the effect of in utero and postnatal exposure on neurodevelopment and subsequent behavioral outcomes. Methods: Using a preclinical rodent model that mimics oxy exposure in utero (IUO) and postnatally (PNO), we employed an integrative holistic systems biology approach encompassing proton magnetic resonance spectroscopy (¹H-MRS), electrophysiology, RNA-sequencing, and Von Frey pain testing to elucidate molecular and behavioral changes in the exposed offspring during early neurodevelopment as well as adulthood. Results: ¹H-MRS studies revealed significant changes in key brain metabolites in the exposed offspring that were corroborated with changes in synaptic currents. Transcriptomic analysis employing RNA-sequencing identified alterations in the expression of pivotal genes associated with synaptic transmission, neurodevelopment, mood disorders, and addiction in the treatment groups. Furthermore, Von Frey analysis revealed lower pain thresholds in both exposed groups. Conclusions: Given the increased use of opiates, understanding the persistent developmental effects of these drugs on children will delineate potential risks associated with opiate use beyond the direct effects in pregnant women.

DOI Link

10.3389/fcell.2020.619199

ISSN

2296-634X

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Recommended Citation

Odegaard, Katherine E.; Schaal, Victoria L.; Clark, Alexander R.; Koul, Sneh; Sankarasubramanian, Jagadesan; Xia, Zhiqiu; Mellon, Melissa; Uberti, Mariano; Liu, Yutong; Stothert, Andrew; Van Hook, Matthew J.; Wang, Han-Jun; Guda, Chittibabu; Lisco, Steven J.; Pendyala, Gurudutt; and Yelamanchili, Sowmya V., "A Holistic Systems Approach to Characterize the Impact of Pre- and Post-natal Oxycodone Exposure on Neurodevelopment and Behavior" (2021). Journal Articles: Anesthesiology. 7.
https://digitalcommons.unmc.edu/com_anesth_articles/7