TY - JOUR
T1 - A Holistic Systems Approach to Characterize the Impact of Pre- and Post-natal Oxycodone Exposure on Neurodevelopment and Behavior
AU - Odegaard, Katherine E.
AU - Schaal, Victoria L.
AU - Clark, Alexander R.
AU - Koul, Sneh
AU - Sankarasubramanian, Jagadesan
AU - Xia, Zhiqiu
AU - Mellon, Melissa
AU - Uberti, Mariano
AU - Liu, Yutong
AU - Stothert, Andrew
AU - Van Hook, Matthew
AU - Wang, Hanjun
AU - Guda, Chittibabu
AU - Lisco, Steven J.
AU - Pendyala, Gurudutt
AU - Yelamanchili, Sowmya V.
N1 - Publisher Copyright:
© Copyright © 2021 Odegaard, Schaal, Clark, Koul, Sankarasubramanian, Xia, Mellon, Uberti, Liu, Stothert, Van Hook, Wang, Guda, Lisco, Pendyala and Yelamanchili.
PY - 2021/1/7
Y1 - 2021/1/7
N2 - 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.
AB - 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.
KW - RNA-sequencing (RNA-Seq)
KW - Von Frey
KW - electrophysiology
KW - oxycodone
KW - proton magnetic resonance spectroscopy (1H-MRS)
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U2 - 10.3389/fcell.2020.619199
DO - 10.3389/fcell.2020.619199
M3 - Article
C2 - 33490084
AN - SCOPUS:85099727647
SN - 2296-634X
VL - 8
JO - Frontiers in Cell and Developmental Biology
JF - Frontiers in Cell and Developmental Biology
M1 - 619199
ER -