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

• Published in: Neurochemical research 2018-12, Vol.43 (12), p.2460-2472
• Main Authors: Hwang, Seojin, Lee, Seong-eun, Ahn, Sang-Gun, Lee, Gum Hwa
• Format: Article
• Language: English
• Subjects: Activation; Animals; Benzofurans - pharmacology; Biochemistry; Biomedical and Life Sciences; Biomedicine; c-Fos protein; Calcium; Calcium (extracellular); Calcium influx; Cascades; Cell Biology; Cells, Cultured; Cerebral Cortex - cytology; Cerebral Cortex - drug effects; Cerebral Cortex - metabolism; Coumarins - pharmacology; Dose-Response Relationship, Drug; EGR-1 protein; Female; Gene Expression; Genes; Genes, Immediate-Early - drug effects; Genes, Immediate-Early - physiology; Glutamic acid receptors (ionotropic); Hippocampus; Immediate-early proteins; Intracellular; Intracellular signalling; Kinases; MAP kinase; Memory; Mice; Mice, Inbred ICR; N-Methyl-D-aspartic acid receptors; Neurochemistry; Neurology; Neuronal Plasticity - drug effects; Neuronal Plasticity - physiology; Neurons; Neurons - drug effects; Neurons - metabolism; Neurosciences; Original Paper; Pregnancy; Protein kinase; Proteins; Receptor mechanisms; Receptors; Seeds; Synapses; Synapses - drug effects; Synapses - metabolism; Synaptic plasticity
• ISSN: 0364-3190; 1573-6903
• DOI: 10.1007/s11064-018-2674-9

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 EC 50 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.