Department of Biophysics and Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo Tokyo, Japan ; Bioinformatics Project of Japan Science and Technology Agency, The University of Tokyo Tokyo, Japan.
Department of Biophysics and Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo Tokyo, Japan ; Department of Physics, College of Science and Technology, Nihon University Chiyoda, Tokyo, Japan.
Front Neural Circuits. 2013 Nov 27;7:191. doi: 10.3389/fncir.2013.00191. eCollection 2013.
Modulation of synapses under acute stress is attracting much attention. Exposure to acute stress induces corticosterone (CORT) secretion from the adrenal cortex, resulting in rapid increase of CORT levels in plasma and the hippocampus. We tried to test whether rapid CORT effects involve activation of essential kinases as non-genomic processes. We demonstrated rapid effects (~1 h) of CORT on the density of thorns, by imaging Lucifer Yellow-injected neurons in adult male rat hippocampal slices. Thorns of thorny excrescences of CA3 hippocampal neurons are post-synaptic regions whose presynaptic partners are mossy fiber terminals. The application of CORT at 100, 500, and 1000 nM induced a rapid increase in the density of thorns in the stratum lucidum of CA3 pyramidal neurons. Co-administration of RU486, an antagonist of glucocorticoid receptor (GR), abolished the effect of CORT. Blocking a single kinase, including MAPK, PKA, or PKC, suppressed CORT-induced enhancement of thorn-genesis. On the other hand, GSK-3β was not involved in the signaling of thorn-genesis. Blocking AMPA receptors suppressed the CORT effect. Expression of CA3 synaptic/extranuclear GR was demonstrated by immunogold electron microscopic analysis. From these results, stress levels of CORT (100-1000 nM) might drive the rapid thorn-genesis via synaptic/extranuclear GR and multiple kinase pathways, although a role of nuclear GRs cannot be completely excluded.
急性应激下突触的调节引起了广泛关注。急性应激会促使肾上腺皮质分泌皮质酮（CORT），导致血浆和海马中的 CORT 水平迅速升高。我们试图测试快速的 CORT 效应是否涉及激活必需激酶作为非基因组过程。我们通过对成年雄性大鼠海马切片中注射 Lucifer Yellow 的神经元进行成像，证明了 CORT 对棘密度的快速作用（~1 小时）。CA3 海马神经元的棘状突起的棘是突触后区域，其突触前伙伴是苔藓纤维末梢。应用 100、500 和 1000 nM 的 CORT 会快速增加 CA3 锥体神经元层状 lucidum 中的棘密度。同时给予 RU486（糖皮质激素受体（GR）拮抗剂）会消除 CORT 的作用。阻断单一激酶，包括 MAPK、PKA 或 PKC，会抑制 CORT 诱导的棘生成增强。另一方面，GSK-3β 不参与棘生成的信号转导。阻断 AMPA 受体会抑制 CORT 效应。免疫金电子显微镜分析显示 CA3 突触/核外 GR 的表达。从这些结果来看，CORT（100-1000 nM）的应激水平可能通过突触/核外 GR 和多种激酶途径驱动快速的棘生成，尽管不能完全排除核 GRs 的作用。
