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Genetic Up-Regulation or Pharmacological Activation of the Na+/Ca2+ Exchanger 1 (NCX1) Enhances Hippocampal-Dependent Contextual and Spatial Learning and Memory.
Molecular Neurobiology ( IF 5.1 ) Pub Date : 2020-02-11 , DOI: 10.1007/s12035-020-01888-4
Silvia Natale 1 , Serenella Anzilotti 2 , Tiziana Petrozziello 1 , Roselia Ciccone 1 , Angelo Serani 1 , Lucrezia Calabrese 1 , Beatrice Severino 3 , Francesco Frecentese 3 , Agnese Secondo 1 , Anna Pannaccione 1 , Ferdinando Fiorino 3 , Ornella Cuomo 1 , Antonio Vinciguerra 1 , Lucia D'Esposito 1 , Adolfo Gustavo Sadile 4 , Simona Cabib 5 , Gianfranco Di Renzo 1 , Lucio Annunziato 2 , Pasquale Molinaro 1
Affiliation  

The Na+/Ca2+ exchanger 1 (NCX1) participates in the maintenance of neuronal Na+ and Ca2+ homeostasis, and it is highly expressed at synapse level of some brain areas involved in learning and memory processes, including the hippocampus, cortex, and amygdala. Furthermore, NCX1 increases Akt1 phosphorylation and enhances glutamate-mediated Ca2+ influx during depolarization in hippocampal and cortical neurons, two processes involved in learning and memory mechanisms. We investigated whether the modulation of NCX1 expression/activity might influence learning and memory processes. To this aim, we used a knock-in mouse overexpressing NCX1 in hippocampal, cortical, and amygdala neurons (ncx1.4over) and a newly synthesized selective NCX1 stimulating compound, named CN-PYB2. Both ncx1.4over and CN-PYB2-treated mice showed an amelioration in spatial learning performance in Barnes maze task, and in context-dependent memory consolidation after trace fear conditioning. On the other hand, these mice showed no improvement in novel object recognition task which is mainly dependent on non-spatial memory and displayed an increase in the active phosphorylated CaMKIIα levels in the hippocampus. Interestingly, both of these mice showed an increased level of context-dependent anxiety.Altogether, these results demonstrate that neuronal NCX1 participates in spatial-dependent hippocampal learning and memory processes.

中文翻译:

Na+/Ca2+ 交换剂 1 (NCX1) 的基因上调或药理学激活增强了海马依赖的上下文和空间学习和记忆。

Na+/Ca2+ 交换器 1 (NCX1) 参与维持神经元 Na+ 和 Ca2+ 稳态,在涉及学习和记忆过程的一些大脑区域的突触水平上高度表达,包括海马、皮质和杏仁核。此外,NCX1 在海马和皮层神经元的去极化过程中增加 Akt1 磷酸化并增强谷氨酸介导的 Ca2+ 流入,这两个过程涉及学习和记忆机制。我们研究了 NCX1 表达/活性的调节是否会影响学习和记忆过程。为此,我们使用了在海马、皮质和杏仁核神经元 (ncx1.4over) 中过表达 NCX1 的敲入小鼠和新合成的选择性 NCX1 刺激化合物 CN-PYB2。两个ncx1。4over 和 CN-PYB2 处理的小鼠在 Barnes 迷宫任务中的空间学习表现以及在追踪恐惧条件反射后的情境依赖性记忆巩固方面表现出改善。另一方面,这些小鼠在新的物体识别任务中没有表现出任何改善,这主要依赖于非空间记忆,并且表现出海马体中活性磷酸化 CaMKIIα 水平的增加。有趣的是,这两只老鼠都表现出更高水平的情境依赖性焦虑。总之,这些结果表明神经元 NCX1 参与了空间依赖性海马学习和记忆过程。这些小鼠在新的物体识别任务中没有表现出任何改善,这主要依赖于非空间记忆,并且显示出海马体中活性磷酸化 CaMKIIα 水平的增加。有趣的是,这两只老鼠都表现出更高水平的情境依赖性焦虑。总之,这些结果表明神经元 NCX1 参与了空间依赖性海马学习和记忆过程。这些小鼠在新的物体识别任务中没有表现出任何改善,这主要依赖于非空间记忆,并且显示出海马体中活性磷酸化 CaMKIIα 水平的增加。有趣的是,这两只老鼠都表现出更高水平的情境依赖性焦虑。总之,这些结果表明神经元 NCX1 参与了空间依赖性海马学习和记忆过程。
更新日期:2020-04-22
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