Development of Anxiety-Like Behavior via Hippocampal IGF-2 Signaling in the Offspring of Parental Morphine Exposure: Effect of Enriched Environment
Development of Anxiety-Like Behavior via Hippocampal IGF-2 Signaling in the Offspring of Parental Morphine Exposure: Effect of Enriched Environment
复制标题
父母吗啡暴露后代通过海马 IGF-2 信号传导产生焦虑样行为：丰富环境的影响
DOI：
10.1038/npp.2014.128
复制
发表时间：
2014-11-01
影响因子：
7.6
通讯作者：
Dai, Ru-Ping
中科院分区：
文献类型：
--
作者：
Li, Chang-Qi;Luo, Yan-Wei;Dai, Ru-Ping
阿片成瘾是世界范围内的重大社会、经济和医学问题。长期接触阿片类药物的长期不良后果不仅涉及个人本身，而且还涉及他们的后代。青春期母亲接触吗啡会导致成年后代的行为和大脑形态发生变化。然而，很少有研究调查成年鸦片类药物暴露对其后代的影响。此外，调控吗啡暴露的代际影响的潜在分子信号仍然难以捉摸。我们在这里报道了成年雄性和雌性大鼠暴露吗啡导致其成年后代海马齿状回(DG)区出现焦虑样行为和树突回缩。行为和形态的改变伴随着DG颗粒区胰岛素样生长因子-2信号的下调。通过双侧DG内注射编码IGF-2基因的慢病毒，使海马区IGF-2过表达，可以防止子代出现类似焦虑的行为。此外，青春期暴露在丰富的环境中纠正了成年后代海马区IGF-2表达的减少、焦虑样行为的正常化和树突回缩。因此，父母吗啡暴露可导致海马IGF-2表达下调，从而导致其后代焦虑和海马树突状回缩。青春期丰富的环境经验通过海马体IGF-2信号阻止了他们后代的行为和形态变化。IGF-2和丰富的环境可能是预防父母接触阿片类药物的子代焦虑和脑萎缩的潜在干预措施。
Opioid addiction is a major social, economic, and medical problem worldwide. Long-term adverse consequences of chronic opiate exposure not only involve the individuals themselves but also their offspring. Adolescent maternal morphine exposure results in behavior and morphologic changes in the brain of their adult offspring. However, few studies investigate the effect of adult opiate exposure on their offspring. Furthermore, the underlying molecular signals regulating the intergenerational effects of morphine exposure are still elusive. We report here that morphine exposure of adult male and female rats resulted in anxiety-like behavior and dendritic retraction in the dentate gyrus (DG) region of the hippocampus in their adult offspring. The behavior and morphologic changes were concomitant with the downregulation of insulin-like growth factor (IGF)-2 signaling in the granular zone of DG. Overexpression of hippocampal IGF-2 by bilateral intra-DG injection of lentivirus encoding the IGF-2 gene prevented anxiety-like behaviors in the offspring. Furthermore, exposure to an enriched environment during adolescence corrected the reduction of hippocampal IGF-2 expression, normalized anxiety-like behavior and reversed dendritic retraction in the adult offspring. Thus, parental morphine exposure can lead to the downregulation of hippocampal IGF-2, which contributed to the anxiety and hippocampal dendritic retraction in their offspring. An adolescent-enriched environment experience prevented the behavior and morphologic changes in their offspring through hippocampal IGF-2 signaling. IGF-2 and an enriched environment may be a potential intervention to prevention of anxiety and brain atrophy in the offspring of parental opioid exposure.