Argyrousi Elentina K, Heckman Pim R A, Prickaerts Jos
Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University, Maastricht, 6200 MD, the Netherlands.
Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University, Maastricht, 6200 MD, the Netherlands.
Neurosci Biobehav Rev. 2020 Jun;113:12-38. doi: 10.1016/j.neubiorev.2020.02.004. Epub 2020 Feb 7.
A plethora of studies indicate the important role of cAMP and cGMP cascades in neuronal plasticity and memory function. As a result, altered cyclic nucleotide signaling has been implicated in the pathophysiology of mnemonic dysfunction encountered in several diseases. In the present review we provide a wide overview of studies regarding the involvement of cyclic nucleotides, as well as their upstream and downstream molecules, in physiological and pathological mnemonic processes. Next, we discuss the regulation of the intracellular concentration of cyclic nucleotides via phosphodiesterases, the enzymes that degrade cAMP and/or cGMP, and via A-kinase-anchoring proteins that refine signal compartmentalization of cAMP signaling. We also provide an overview of the available data pointing to the existence of specific time windows in cyclic nucleotide signaling during neuroplasticity and memory formation and the significance to target these specific time phases for improving memory formation. Finally, we highlight the importance of emerging imaging tools like Förster resonance energy transfer imaging and optogenetics in detecting, measuring and manipulating the action of cyclic nucleotide signaling cascades.
大量研究表明，环磷酸腺苷（cAMP）和环磷酸鸟苷（cGMP）信号级联在神经元可塑性和记忆功能中发挥着重要作用。因此，环核苷酸信号的改变与多种疾病中出现的记忆功能障碍的病理生理学有关。在本综述中，我们广泛概述了有关环核苷酸及其上游和下游分子在生理和病理记忆过程中的参与情况的研究。接下来，我们讨论通过磷酸二酯酶（降解cAMP和/或cGMP的酶）以及通过优化cAMP信号的信号分隔的A激酶锚定蛋白对环核苷酸细胞内浓度的调节。我们还概述了现有数据，这些数据表明在神经可塑性和记忆形成过程中环核苷酸信号存在特定的时间窗口，以及针对这些特定时间阶段以改善记忆形成的重要性。最后，我们强调了诸如Förster共振能量转移成像和光遗传学等新兴成像工具在检测、测量和操纵环核苷酸信号级联作用方面的重要性。
