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Psoralidin Stimulates Expression of Immediate-Early Genes and Synapse Development in Primary Cortical Neurons

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Abstract

Upon synaptic stimulation and glutamate release, glutamate receptors are activated to regulate several downstream effectors and signaling pathways resulting in synaptic modification. One downstream intracellular effect, in particular, is the expression of immediate-early genes (IEGs), which have been proposed to be important in synaptic plasticity because of their rapid expression following synaptic activation and key role in memory formation. In this study, we screened a natural compound library in order to find a compound that could induce the expression of IEGs in primary cortical neurons and discovered that psoralidin, a natural compound isolated from the seeds of Psoralea corylifolia, stimulated synaptic modulation. Psoralidin activated mitogen-activated protein kinase (MAPK) signaling, which in turn induced the expression of neuronal IEGs, particularly Arc, Egr-1, and c-fos. N-methyl-d-aspartate (NMDA) receptors activation and extracellular calcium influx were implicated in the psoralidin-induced intracellular changes. In glutamate dose–response curve, psoralidin shifted glutamate EC50 to lower values without enhancing maximum activity. Interestingly, psoralidin increased the density, area, and intensity of excitatory synapses in primary hippocampal neurons, which were mediated by NMDA receptor activation and MAPK signaling. These results suggest that psoralidin triggers synaptic remodeling through activating NMDA receptor and subsequent MAPK signaling cascades and therefore could possibly serve as an NMDA receptor modulator.

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Change history

  • 01 December 2018

    The original version of this article unfortunately contained a mistake. The funding information was incorrect in the Acknowledgement section of this article. The corrected text is given below.

  • 01 December 2018

    The original version of this article unfortunately contained a mistake. The funding information was incorrect in the Acknowledgement section of this article. The corrected text is given below.

  • 01 December 2018

    The original version of this article unfortunately contained a mistake. The funding information was incorrect in the Acknowledgement section of this article. The corrected text is given below.

Abbreviations

IEGs:

Immediate-early genes

MAPK:

Mitogen-activated protein kinase

NMDA:

N-methyl-d-aspartate

ANOVA:

Analysis of variance

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Acknowledgements

This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2018R1D1A1B07043710). This study was also supported by a research fund from Chosun University (2015, K207134001).

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Correspondence to Gum Hwa Lee.

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Hwang, S., Lee, Se., Ahn, SG. et al. Psoralidin Stimulates Expression of Immediate-Early Genes and Synapse Development in Primary Cortical Neurons. Neurochem Res 43, 2460–2472 (2018). https://doi.org/10.1007/s11064-018-2674-9

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