Epigenetic inheritance of a cocaine-resistance phenotype.
Epigenetic inheritance of a cocaine-resistance phenotype.
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DOI：
10.1038/nn.3280
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发表时间：
2013-01
影响因子：
25
通讯作者：
Pierce, R Christopher
中科院分区：
文献类型：
--
作者：
Vassoler, Fair M.;White, Samantha L.;Schmidt, Heath D.;Sadri-Vakili, Ghazaleh;Pierce, R Christopher
描述了大鼠可卡因自我给药引起的可遗传表型。我们观察到延迟收购和减少维护可卡因自我管理的男性，但不是女性，后代的父系，自我管理可卡因。脑源性神经营养因子（BDNF）的mRNA和蛋白质增加，在内侧前额叶皮层（mPFC）和有一个增加的协会乙酰化组蛋白H3与BDNF的启动子，只有在可卡因经验丰富的公畜的雄性后代。BDNF受体拮抗剂（TrkB受体拮抗剂ANA-12）的管理扭转减少可卡因自我管理的雄性可卡因sired大鼠。此外，乙酰化组蛋白H3与BDNF启动子的关联在自我施用可卡因的公畜的精子中增加。总的来说，这些研究结果表明，自愿的父亲摄入可卡因的结果在生殖细胞的表观遗传重编程，导致深远的影响mPFC基因的表达和抗性的可卡因加固男性后代。
A heritable phenotype resulting from the self-administration of cocaine in rats was delineated. We observed delayed acquisition and reduced maintenance of cocaine self-administration in male, but not female, offspring of sires that self-administered cocaine. Brain-derived neurotrophic factor (BDNF) mRNA and protein were increased in the medial prefrontal cortex (mPFC) and there was an increased association of acetylated histone H3 with BDNF promoters only in the male offspring of cocaine-experienced sires. Administration of a BDNF receptor antagonist (the TrkB receptor antagonist ANA-12) reversed the diminished cocaine self-administration in male cocaine-sired rats. In addition, the association of acetylated histone H3 with BDNF promoters was increased in the sperm of sires that self-administered cocaine. Collectively, these findings indicate that voluntary paternal ingestion of cocaine results in epigenetic reprograming of the germline resulting in profound effects on mPFC gene expression and resistance to cocaine reinforcement in male offspring.
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影响因子：
10.6
作者：
Alter MD;Gilani AI;Champagne FA;Curley JP;Turner JB;Hen R
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作者：
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通讯作者：
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