Journal
NEUROPHARMACOLOGY
Volume 131, Issue -, Pages 68-82Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuropharm.2017.12.014
Keywords
Syringaresinol; Excitatory synapse; Presynaptic suppression; Readily releasable pool; Antiepileptic activity
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Funding
- Brain Korea 21 Plus Program
- Korean Health Technology R&D Project, Ministry of Health and Welfare [A111587]
- National Research Foundation of Korea - Ministry of Education, Science and Technology [2014R1A1A2059880, 2017M3C7A1029611, 2017R1D1A1B03032935]
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Many neuromodulating drugs acting on the nervous system originate from botanical sources. These plant-derived substances modulate the activity of receptors, ion channels, or transporters in neurons. Their properties make the substances useful for medicine and research. Here, we show that the plant lignan (+)-syringaresinol (SYR) suppresses excitatory synaptic transmission via presynaptic modulation. Bath application of SYR rapidly reduced the slopes of the field excitatory postsynaptic potentials (fEPSPs) at the hippocampal Schaffer collateral (SC)-CA1 synapse in a dose-dependent manner. SYR preferentially affected excitatory synapses, while inhibitory synaptic transmission remained unchanged. SYR had no effect on the conductance or the desensitization of AMPARs but increased the paired -pulse ratios of synaptic responses at short (20-200 ms) inter-stimulus intervals. These presynaptic changes were accompanied by a reduction of the readily releasable pool size. Pretreatment of hippocampal slices with the Go protein inhibitor N-ethylmaleimide (NEM) abolished the effect of SYR on excitatory synaptic transmission, while the application of SYR significantly decreased Ca2+ currents and hyperpolarized the resting membrane potentials of hippocampal neurons. In addition, SYR suppressed picrotoxin-induced epileptiform activity in hippocampal slices. Overall, our study identifies SYR as a new neuromodulating agent and suggests that SYR suppresses excitatory synaptic transmission by modulating presynaptic transmitter release. (C) 2017 Elsevier Ltd. All rights reserved.
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