Puberty marks major changes in the hippocampal and cortical c-Fos activation pattern induced by NMDA receptor antagonists
Puberty marks major changes in the hippocampal and cortical c-Fos activation pattern induced by NMDA receptor antagonists
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DOI：
10.1016/j.neuropharm.2016.03.023
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发表时间：
2017-01-01
影响因子：
4.7
通讯作者：
Gass, Peter
中科院分区：
文献类型：
--
作者：
Inta, Ioana;Domonkos, Emese;Gass, Peter
非选择性和亚基 (GluN2B) 特异性 N-甲基-D-天冬氨酸受体 (NMDAR) 拮抗剂是有前途的替代抗抑郁药物，具有快速起效的作用。 NMDAR 拮抗剂诱导的神经元激活模式仅在成年啮齿动物大脑中通过 c-Fos 表达分析得到了很好的表征。相比之下，关于它们在产后发育过程中的影响的信息很少。在这里，我们对出生后第 16 天 (P16) 到 P40 的非选择性 NMDAR 拮抗剂 MK-801 和 GluN2B 特异性拮抗剂 Ro 25-6981 进行了系统的 c-Fos 脑图谱分析。我们发现与成人相比，激活模式存在显着的性别特异性区域差异。令人惊讶的是，在海马体中，MK-801 在青春期前阶段（尤其是 P24）触发了非常强的 c-Fos 表达，随后在 P30（小鼠青春期开始的大致时间点）后出现低水平表达。青春期前 MK-801 触发的 c-Fos 表达的皮质分布也与成人大脑有很大不同，仅在青春期前阶段的深层皮质层显示出高水平。相比之下，Ro 25-6981 诱导的皮质激活从青春期前的高水平减少，并且与海马中 MK-801 触发的低水平相比。这些结果揭示了青春期期间 NMDAR 拮抗剂诱导的 c-Fos 激活模式的高度动态变化。本文是题为“离子型谷氨酸受体”的特刊的一部分。 (C) 2016 Elsevier Ltd. 保留所有权利。
Non-selective and subunit (GluN2B)-specific N-methyl-D-aspartate receptor (NMDAR) antagonists represent promising alternative antidepressant drugs with fast onset of the therapeutic action. The neuronal activation pattern induced by NMDAR antagonists is well characterized by c-Fos expression analysis only in the adult rodent brain. In contrast, there is little information available regarding their effects during postnatal development. Here we performed a systematic c-Fos brain mapping of the non-selective NMDAR antagonist MK-801 and the GluN2B-specific antagonist Ro 25-6981 from postnatal day 16 (P16) to P40. We found significant regional differences with gender-specificity in the activation pattern compared to the adult. Surprisingly, in the hippocampus, MK-801 triggered at pre-pubertal stages (especially at P24) very strong c-Fos expression, followed by low levels after P30, the approximate time point of puberty onset in mice. The cortical distribution of MK-801-triggered c-Fos expression before puberty differed also substantially from the adult brain, showing high levels only in deep cortical layers at pre-pubertal stages. In comparison, the cortical activation induced by Ro 25-6981 diminished from high pre-pubertal levels and was in comparison with that triggered by MK-801 low in the hippocampus. These results reveal highly dynamic changes in the c-Fos activation pattern induced by NMDAR antagonists during puberty. This article is part of the Special Issue entitled 'Ionotropic glutamate receptors'. (C) 2016 Elsevier Ltd. All rights reserved.