Mitochondria-Related Nuclear Gene Expression in the Nucleus Accumbens and Blood Mitochondrial Copy Number After Developmental Fentanyl Exposure in Adolescent Male and Female C57BL/6 Mice

The potency of the synthetic opioid fentanyl and its increased clinical availability has led to the rapid escalation of use in the general population, increased recreational exposure, and subsequently opioid-related overdoses. The wide-spread use of fentanyl has, consequently, increased the incidenc...

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Autores principales:	Cali A. Calarco, Megan E. Fox, Saskia Van Terheyden, Makeda D. Turner, Jason B. Alipio, Ramesh Chandra, Mary Kay Lobo
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	mitochondria mitochondrial copy number developmental drug exposure fentanyl nucleus accumbens gene expression Psychiatry RC435-571
Acceso en línea:	https://doaj.org/article/6a32ccad24e64c72be590cb3f98c0f71
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spelling	oai:doaj.org-article:6a32ccad24e64c72be590cb3f98c0f712021-11-18T07:16:29ZMitochondria-Related Nuclear Gene Expression in the Nucleus Accumbens and Blood Mitochondrial Copy Number After Developmental Fentanyl Exposure in Adolescent Male and Female C57BL/6 Mice1664-064010.3389/fpsyt.2021.737389https://doaj.org/article/6a32ccad24e64c72be590cb3f98c0f712021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fpsyt.2021.737389/fullhttps://doaj.org/toc/1664-0640The potency of the synthetic opioid fentanyl and its increased clinical availability has led to the rapid escalation of use in the general population, increased recreational exposure, and subsequently opioid-related overdoses. The wide-spread use of fentanyl has, consequently, increased the incidence of in utero exposure to the drug, but the long-term effects of this type of developmental exposure are not yet understood. Opioid use has also been linked to reduced mitochondrial copy number in blood in clinical populations, but the link between this peripheral biomarker and genetic or functional changes in reward-related brain circuitry is still unclear. Additionally, mitochondrial-related gene expression in reward-related brain regions has not been examined in the context of fentanyl exposure, despite the growing literature demonstrating drugs of abuse impact mitochondrial function, which subsequently impacts neuronal signaling. The current study uses exposure to fentanyl via dam access to fentanyl drinking water during gestation and lactation as a model for developmental drug exposure. This perinatal drug-exposure is sufficient to impact mitochondrial copy number in circulating blood leukocytes, as well as mitochondrial-related gene expression in the nucleus accumbens (NAc), a reward-related brain structure, in a sex-dependent manner in adolescent offspring. Specific NAc gene expression is correlated with both blood mitochondrial copy number and with anxiety related behaviors dependent on developmental exposure to fentanyl and sex. These data indicate that developmental fentanyl exposure impacts mitochondrial function in both the brain and body in ways that can impact neuronal signaling and may prime the brain for altered reward-related behavior in adolescence and later into adulthood.Cali A. CalarcoMegan E. FoxSaskia Van TerheydenMakeda D. TurnerJason B. AlipioRamesh ChandraMary Kay LoboFrontiers Media S.A.articlemitochondriamitochondrial copy numberdevelopmental drug exposurefentanylnucleus accumbensgene expressionPsychiatryRC435-571ENFrontiers in Psychiatry, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	mitochondria mitochondrial copy number developmental drug exposure fentanyl nucleus accumbens gene expression Psychiatry RC435-571
spellingShingle	mitochondria mitochondrial copy number developmental drug exposure fentanyl nucleus accumbens gene expression Psychiatry RC435-571 Cali A. Calarco Megan E. Fox Saskia Van Terheyden Makeda D. Turner Jason B. Alipio Ramesh Chandra Mary Kay Lobo Mitochondria-Related Nuclear Gene Expression in the Nucleus Accumbens and Blood Mitochondrial Copy Number After Developmental Fentanyl Exposure in Adolescent Male and Female C57BL/6 Mice
description	The potency of the synthetic opioid fentanyl and its increased clinical availability has led to the rapid escalation of use in the general population, increased recreational exposure, and subsequently opioid-related overdoses. The wide-spread use of fentanyl has, consequently, increased the incidence of in utero exposure to the drug, but the long-term effects of this type of developmental exposure are not yet understood. Opioid use has also been linked to reduced mitochondrial copy number in blood in clinical populations, but the link between this peripheral biomarker and genetic or functional changes in reward-related brain circuitry is still unclear. Additionally, mitochondrial-related gene expression in reward-related brain regions has not been examined in the context of fentanyl exposure, despite the growing literature demonstrating drugs of abuse impact mitochondrial function, which subsequently impacts neuronal signaling. The current study uses exposure to fentanyl via dam access to fentanyl drinking water during gestation and lactation as a model for developmental drug exposure. This perinatal drug-exposure is sufficient to impact mitochondrial copy number in circulating blood leukocytes, as well as mitochondrial-related gene expression in the nucleus accumbens (NAc), a reward-related brain structure, in a sex-dependent manner in adolescent offspring. Specific NAc gene expression is correlated with both blood mitochondrial copy number and with anxiety related behaviors dependent on developmental exposure to fentanyl and sex. These data indicate that developmental fentanyl exposure impacts mitochondrial function in both the brain and body in ways that can impact neuronal signaling and may prime the brain for altered reward-related behavior in adolescence and later into adulthood.
format	article
author	Cali A. Calarco Megan E. Fox Saskia Van Terheyden Makeda D. Turner Jason B. Alipio Ramesh Chandra Mary Kay Lobo
author_facet	Cali A. Calarco Megan E. Fox Saskia Van Terheyden Makeda D. Turner Jason B. Alipio Ramesh Chandra Mary Kay Lobo
author_sort	Cali A. Calarco
title	Mitochondria-Related Nuclear Gene Expression in the Nucleus Accumbens and Blood Mitochondrial Copy Number After Developmental Fentanyl Exposure in Adolescent Male and Female C57BL/6 Mice
title_short	Mitochondria-Related Nuclear Gene Expression in the Nucleus Accumbens and Blood Mitochondrial Copy Number After Developmental Fentanyl Exposure in Adolescent Male and Female C57BL/6 Mice
title_full	Mitochondria-Related Nuclear Gene Expression in the Nucleus Accumbens and Blood Mitochondrial Copy Number After Developmental Fentanyl Exposure in Adolescent Male and Female C57BL/6 Mice
title_fullStr	Mitochondria-Related Nuclear Gene Expression in the Nucleus Accumbens and Blood Mitochondrial Copy Number After Developmental Fentanyl Exposure in Adolescent Male and Female C57BL/6 Mice
title_full_unstemmed	Mitochondria-Related Nuclear Gene Expression in the Nucleus Accumbens and Blood Mitochondrial Copy Number After Developmental Fentanyl Exposure in Adolescent Male and Female C57BL/6 Mice
title_sort	mitochondria-related nuclear gene expression in the nucleus accumbens and blood mitochondrial copy number after developmental fentanyl exposure in adolescent male and female c57bl/6 mice
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/6a32ccad24e64c72be590cb3f98c0f71
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Mitochondria-Related Nuclear Gene Expression in the Nucleus Accumbens and Blood Mitochondrial Copy Number After Developmental Fentanyl Exposure in Adolescent Male and Female C57BL/6 Mice

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