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.
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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DOI：
10.3389/fpsyt.2021.737389
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发表时间：
2021
影响因子：
4.7
通讯作者：
Lobo MK
中科院分区：
文献类型：
--
作者：
Calarco CA;Fox ME;Van Terheyden S;Turner MD;Alipio JB;Chandra R;Lobo MK
合成阿片类芬太尼的效力及其临床可用性的增加导致了普通人群中使用的快速升级，增加了娱乐性暴露，以及随后的阿片类药物相关过量。因此，芬太尼的广泛使用增加了宫内暴露于该药物的发生率，但这种发育暴露的长期影响尚未了解。阿片类药物的使用也与临床人群中血液中线粒体拷贝数的减少有关，但这种外周生物标志物与奖励相关脑回路中的遗传或功能变化之间的联系尚不清楚。此外，在芬太尼暴露的背景下，尚未检查奖励相关脑区中的奖赏相关基因表达，尽管越来越多的文献表明滥用药物影响线粒体功能，随后影响神经元信号传导。目前的研究使用暴露于芬太尼通过大坝获得芬太尼饮用水在妊娠期和哺乳期作为一个模型的发育药物暴露。这种围产期药物暴露足以以性别依赖性方式影响青春期后代循环血液白细胞中的线粒体拷贝数，以及伏隔核（NAc）（一种与奖励相关的大脑结构）中线粒体相关的基因表达。特异性NAc基因表达与血液线粒体拷贝数和依赖于芬太尼和性别的发育暴露的焦虑相关行为相关。这些数据表明，发育中的芬太尼暴露会影响大脑和身体的线粒体功能，从而影响神经元信号传导，并可能使大脑在青春期和成年期改变奖励相关行为。
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.
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影响因子：
3.6
作者：
Cole SL;Chandra R;Harris M;Patel I;Wang T;Kim H;Jensen L;Russo SJ;Turecki G;Gancarz-Kausch AM;Dietz DM;Lobo MK
通讯作者：
Lobo MK
影响因子：
1.5
作者：
Chen VS;Morrison JP;Southwell MF;Foley JF;Bolon B;Elmore SA
通讯作者：
Elmore SA
DOI：
10.1096/fj.202100067r
发表时间：
2021-06
期刊：
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
影响因子：
--
作者：
Adebayo M;Singh S;Singh AP;Dasgupta S
通讯作者：
Dasgupta S
影响因子：
16.2
作者：
Chandra R;Engeln M;Schiefer C;Patton MH;Martin JA;Werner CT;Riggs LM;Francis TC;McGlincy M;Evans B;Nam H;Das S;Girven K;Konkalmatt P;Gancarz AM;Golden SA;Iñiguez SD;Russo SJ;Turecki G;Mathur BN;Creed M;Dietz DM;Lobo MK
通讯作者：
Lobo MK
影响因子：
5.3
作者：
Abu Y;Roy S
通讯作者：
Roy S