TY - JOUR
T1 - Buprenorphine Exposure Alters the Development and Migration of Interneurons in the Cortex
AU - Nieto-Estévez, Vanesa
AU - Donegan, Jennifer J.
AU - McMahon, Courtney L.
AU - Elam, Hannah B.
AU - Chavera, Teresa A.
AU - Varma, Parul
AU - Berg, Kelly A.
AU - Lodge, Daniel J.
AU - Hsieh, Jenny
N1 - Publisher Copyright:
Copyright © 2022 Nieto-Estévez, Donegan, McMahon, Elam, Chavera, Varma, Berg, Lodge and Hsieh.
PY - 2022/5/4
Y1 - 2022/5/4
N2 - The misuse of opioids has reached epidemic proportions over the last decade, with over 2.1 million people in the United States suffering from substance use disorders related to prescription opioid pain relievers. This increase in opioid misuse affects all demographics of society, including women of child-bearing age, which has led to a rise in opioid use during pregnancy. Opioid use during pregnancy has been associated with increased risk of obstetric complications and adverse neonatal outcomes, including neonatal abstinence syndrome. Currently, opioid use disorder in pregnant women is treated with long-acting opioid agonists, including buprenorphine. Although buprenorphine reduces illicit opioid use during pregnancy and improves infant outcomes at birth, few long-term studies of the neurodevelopmental consequences have been conducted. The goal of the current experiments was to examine the effects of buprenorphine on the development of the cortex using fetal brain tissue, 3D brain cultures, and rodent models. First, we demonstrated that we can grow cortical and subpallial spheroids, which model the cellular diversity, connectivity, and activity of the developing human brain. Next, we show that cells in the developing human cortex express the nociceptin opioid (NOP) receptor and that buprenorphine can signal through this receptor in cortical spheroids. Using subpallial spheroids to grow inhibitory interneurons, we show that buprenorphine can alter interneuron development and migration into the cortex. Finally, using a rodent model of prenatal buprenorphine exposure, we demonstrate that alterations in interneuron distribution can persist into adulthood. Together, these results suggest that more research is needed into the long-lasting consequences of buprenorphine exposure on the developing human brain.
AB - The misuse of opioids has reached epidemic proportions over the last decade, with over 2.1 million people in the United States suffering from substance use disorders related to prescription opioid pain relievers. This increase in opioid misuse affects all demographics of society, including women of child-bearing age, which has led to a rise in opioid use during pregnancy. Opioid use during pregnancy has been associated with increased risk of obstetric complications and adverse neonatal outcomes, including neonatal abstinence syndrome. Currently, opioid use disorder in pregnant women is treated with long-acting opioid agonists, including buprenorphine. Although buprenorphine reduces illicit opioid use during pregnancy and improves infant outcomes at birth, few long-term studies of the neurodevelopmental consequences have been conducted. The goal of the current experiments was to examine the effects of buprenorphine on the development of the cortex using fetal brain tissue, 3D brain cultures, and rodent models. First, we demonstrated that we can grow cortical and subpallial spheroids, which model the cellular diversity, connectivity, and activity of the developing human brain. Next, we show that cells in the developing human cortex express the nociceptin opioid (NOP) receptor and that buprenorphine can signal through this receptor in cortical spheroids. Using subpallial spheroids to grow inhibitory interneurons, we show that buprenorphine can alter interneuron development and migration into the cortex. Finally, using a rodent model of prenatal buprenorphine exposure, we demonstrate that alterations in interneuron distribution can persist into adulthood. Together, these results suggest that more research is needed into the long-lasting consequences of buprenorphine exposure on the developing human brain.
KW - buprenorphine
KW - cortical development
KW - interneurons
KW - opioid misuse disorder
KW - pregnancy
UR - http://www.scopus.com/inward/record.url?scp=85130249170&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85130249170&partnerID=8YFLogxK
U2 - 10.3389/fnmol.2022.889922
DO - 10.3389/fnmol.2022.889922
M3 - Article
C2 - 35600077
AN - SCOPUS:85130249170
SN - 1662-5099
VL - 15
JO - Frontiers in Molecular Neuroscience
JF - Frontiers in Molecular Neuroscience
M1 - 889922
ER -