甲状腺激素调解了早期生活压力对腹部体区域基因表达和行为的影响
Shannon N Bennett1, Austin B Chang1, Forrest D Rogers2
1Princeton Neuroscience Institute, Princeton University, USA.
Hormones and behavior
|December 23, 2023
概括
早期的生活压力暂时破坏甲状腺功能,影响多巴胺神经元发育. 在发育过程中用甲状腺激素治疗雄性小鼠可以防止未来的压力过敏.
科学领域:
- 神经内分泌学神经内分泌学
- 发育神经科学的发展神经科学.
- 行为神经科学 行为神经科学
背景情况:
- 甲状腺激素对大脑发育至关重要,特别是多巴胺神经元的分化和功能.
- 早期生活压力 (ELS) 可以破坏甲状腺激素信号传递,并与情绪障碍有关.
- 对于ELS对甲状腺功能的影响及其对发展多巴胺系统的后果仍然不清楚.
研究的目的:
- 调查甲状腺激素信号是否介导ELS对多巴胺基中脑发育和行为的影响.
- 确定短暂的甲状腺激素补充是否可以预防ELS的长期行为和分子后果.
主要方法:
- 鼠被暴露在生命早期的压力 (ELS) 中,并在出生后的21天 (P21) 和青春期进行评估.
- 测量甲状腺刺激激素 (TSH) 水平以评估甲状腺信号传递.
- 一些ELS小鼠接受了合成甲状腺激素 (levothyroxine, LT4) 的短暂治疗.
- 分析了对成年人压力的敏感性,腹部体区域 (VTA) 的基因表达以及多巴胺神经元标记物.
主要成果:
- 在P21时,ELS在雄性和雌性小鼠中暂时增加了TSH水平,这表明甲状腺信号发生了变化.
- 在雄性小鼠中,青春期的LT4治疗预防了对成年人的压力过敏.
- 在ELS男性中,LT4治疗恢复了一些ELS诱导的VTA基因表达缺陷,并防止了成人压力引起的变化.
- 在雌性小鼠中没有观察到这些效应.
结论:
- 甲状腺激素信号传递作用在ELS和对VTA发育的有害影响之间起到调解作用.
- 在ELS后暂时纠正甲状腺激素信号缺陷可能是一个可行的策略,以防止未来的压力过敏,特别是在男性.
- 在对ELS和甲状腺激素干预的反应中存在性别差异.
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