CaMKIIα knockdown decreases anxiety in the open field and low serotonin-induced upregulation of GluA1 in the basolateral amygdala.
CaMKIIα knockdown decreases anxiety in the open field and low serotonin-induced upregulation of GluA1 in the basolateral amygdala.
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DOI：
10.1016/j.bbr.2016.01.053
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发表时间：
2016-04-15
影响因子：
2.7
通讯作者：
Keele NB
中科院分区：
文献类型：
--
作者：
Tran L;Keele NB
杏仁核的过度激活与焦虑和情绪障碍有关，但确切的潜在机制尚不清楚。我们以前报道，5-羟色胺（5-HT）在杏仁核（BLA）的基底外侧核（5-HT）的消耗，使用多巴胺能神经毒素5，7-二羟色胺（5，7-DHT）增强学习恐惧和增加谷氨酸受体（Glu）在BLA的表达。在这里，我们调查的假设，CaMKII促进焦虑样行为和增加Glu/AMPA受体亚基A1（GluA 1）的表达后，在BLA的5-HT耗尽。将5，7-DHT注入BLA导致旷场试验（OFT）中的焦虑样行为，并增加BLA中CaMKIIα（Thr-286）的磷酸化。使用腺相关病毒（AAV）递送的shRNAi敲低CaMKIIα亚基同时减弱了OFT中的焦虑样行为，并降低了BLA中的GluA 1表达。我们的研究结果表明，CaMKII信号在低5-HT诱导的焦虑和情绪障碍中起着关键作用，可能通过调节BLA中的GluA 1表达。BLA中5-HT耗竭、CaMKII信号通路和GluA表达之间假定关系的分子模型。减少5-HT消除BLA中的紧张性抑制，增加谷氨酸信号传导。神经传递的持续增加升高突触后细胞内钙并激活CaMKII。CaMKII的激活然后增加GluAs的转录和膜表达。
Hyperactivation of the amygdala is implicated in anxiety and mood disorders, but the precise underlying mechanisms are unclear. We previously reported that depletion of serotonin (5-hydroxytryptamine, 5-HT) in the basolateral nucleus of the amygdala (BLA) using the serotonergic neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) potentiated learned fear and increased glutamate receptor (Glu) expression in BLA. Here we investigated the hypothesis that CaMKII facilitates anxiety-like behavior and increased Glu/AMPA receptor subunit A1 (GluA1) expression following depletion of 5-HT in the BLA. Infusion of 5,7-DHT into the BLA resulted in anxiety-like behavior in the open field test (OFT) and increased the phosphorylation of CaMKIIα (Thr-286) in the BLA. Knockdown of the CaMKIIα subunit using adeno-associated virus (AAV)-delivered shRNAi concomitantly attenuated anxiety-like behavior in the OFT and decreased GluA1 expression in the BLA. Our results suggest that the CaMKII signaling plays a key role in low 5-HT-induced anxiety and mood disturbances, potentially through regulation of GluA1 expression in the BLA. Molecular model of the putative relationship between 5-HT depletion, the CaMKII signaling pathway, and GluA expression in the BLA. Decreased 5-HT removes the tonic inhibition in the BLA, increasing glutamate signaling. The sustained increase in neurotransmission elevates postsynaptic intracellular calcium and activates CaMKII. Activation of CaMKII then increases transcription and membrane expression of GluAs.
影响因子：
4
作者：
Karls, Andrew S.;Mynlieff, Michelle
通讯作者：
Mynlieff, Michelle