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Neurochemical Research

, Volume 43, Issue 12, pp 2460–2472 | Cite as

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

  • Seojin Hwang
  • Seong-eun Lee
  • Sang-Gun Ahn
  • Gum Hwa LeeEmail author
Original Paper
  • 51 Downloads

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.

Keywords

Psoralidin NMDA receptor modulator Immediate-early genes Synaptic plasticity Learning and memory 

Abbreviations

IEGs

Immediate-early genes

MAPK

Mitogen-activated protein kinase

NMDA

N-methyl-d-aspartate

ANOVA

Analysis of variance

Notes

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).

Supplementary material

11064_2018_2674_MOESM1_ESM.docx (711 kb)
Supplementary material 1 (DOCX 710 KB)

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Seojin Hwang
    • 1
  • Seong-eun Lee
    • 1
  • Sang-Gun Ahn
    • 2
  • Gum Hwa Lee
    • 1
    Email author
  1. 1.College of PharmacyChosun UniversityGwangjuSouth Korea
  2. 2.Department of Pathology, College of DentistryChosun UniversityGwangjuSouth Korea

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