Department of Pharmacology, Institute of Biomedical Science I University of São Paulo, Room 338, Av. Prof. Lineu Prestes, 1524, ICB I, Cidade Universitária, 05508-900, São Paulo, SP. Brazil.
Department of Physiology, Institute of Bioscience, University of São Paulo, Adress: Rua do Matão, Travessa 14, 101, São Paulo, 05508-090, Brazil.
Neuropharmacology. 2018 Sep 15;140:260-274. doi: 10.1016/j.neuropharm.2018.08.008. Epub 2018 Aug 9.
Previous research shows Ouabain (OUA) to bind Na, K-ATPase, thereby triggering a number of signaling pathways, including the transcription factors NFᴋB and CREB. These transcription factors play a key role in the regulation of BDNF and WNT-β-catenin signaling cascades, which are involved in neuroprotection and memory regulation. This study investigated the effects of OUA (10 nM) in the modulation of the principal signaling pathways involved in morphological plasticity and memory formation in the hippocampus of adult rats. The results show intrahippocampal injection of OUA 10 nM to activate the Wnt/β-Catenin signaling pathway and to increase CREB/BDNF and NFᴋB levels. These effects contribute to important changes in the cellular microenvironment, resulting in enhanced levels of dendritic branching in hippocampal neurons, in association with an improvement in spatial reference memory and the inhibition of long-term memory extinction.
先前的研究表明,哇巴因(OUA)与 Na,K-ATPase 结合,从而触发许多信号通路,包括转录因子 NFᴋB 和 CREB。这些转录因子在调节 BDNF 和 WNT-β-catenin 信号级联中起着关键作用,而后者参与神经保护和记忆调节。本研究探讨了 OUA(10 nM)在调节成年大鼠海马体中形态可塑性和记忆形成的主要信号通路中的作用。结果表明,向海马内注射 10 nM 的 OUA 可激活 Wnt/β-Catenin 信号通路并增加 CREB/BDNF 和 NFᴋB 水平。这些作用有助于细胞微环境的重要变化,导致海马神经元树突分支增加,与空间参考记忆的改善和长时记忆消退的抑制相关。