1.Echinacoside, an active constituent of Herba Cistanche, suppresses epileptiform activity in hippocampal CA3 pyramidal neurons.
Cheng Wei LU ; Shu Kuei HUANG ; Tzu Yu LIN ; Su Jane WANG
The Korean Journal of Physiology and Pharmacology 2018;22(3):249-255
Echinacoside, an active compound in the herb Herba Cistanche, has been reported to inhibit glutamate release. In this study, we investigated the effects of echinacoside on spontaneous excitatory synaptic transmission changes induced by 4-aminopyridine (4-AP), by using the in vitro rat hippocampal slice technique and whole-cell patch clamp recordings from CA3 pyramidal neurons. Perfusion with echinacoside significantly suppressed the 4-AP-induced epileptiform activity in a concentration-dependent manner. Echinacoside reduced 4-AP-induced increase in frequency of spontaneous excitatory postsynaptic currents (sEPSCs) but it did not affect the amplitude of sEPSCs or glutamate-activated currents, implicating a presynaptic mechanism of action. Echinacoside also potently blocked sustained repetitive firing, which is a basic mechanism of antiepileptic drugs. These results suggest that echinacoside exerts an antiepileptic effect on hippocampal CA3 pyramidal neurons by simultaneously decreasing glutamate release and blocking abnormal firing synchronization. Accordingly, our study provides experimental evidence that echinacoside may represent an effective pharmacological agent for treating epilepsy.
4-Aminopyridine
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Animals
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Anticonvulsants
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Cistanche*
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Epilepsy
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Excitatory Postsynaptic Potentials
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Fires
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Glutamic Acid
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Hippocampus
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In Vitro Techniques
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Perfusion
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Pyramidal Cells*
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Rats
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Synaptic Transmission
2.Eupafolin Suppresses P/Q-Type Ca2+ Channels to Inhibit Ca2+ / Calmodulin-Dependent Protein Kinase II and Glutamate Release at Rat Cerebrocortical Nerve Terminals
Anna CHANG ; Chi-Feng HUNG ; Pei-Wen HSIEH ; Horng-Huey KO ; Su-Jane WANG
Biomolecules & Therapeutics 2021;29(6):630-636
Eupafolin, a constituent of the aerial parts of Phyla nodiflora, has neuroprotective property. Because reducing the synaptic release of glutamate is crucial to achieving pharmacotherapeutic effects of neuroprotectants, we investigated the effect of eupafolin on glutamate release in rat cerebrocortical synaptosomes and explored the possible mechanism. We discovered that eupafolin depressed 4-aminopyridine (4-AP)-induced glutamate release, and this phenomenon was prevented in the absence of extracellular calcium. Eupafolin inhibition of glutamate release from synaptic vesicles was confirmed through measurement of the release of the fluorescent dye FM 1-43. Eupafolin decreased 4-AP-induced [Ca2+ ] i elevation and had no effect on synaptosomal membrane potential. The inhibition of P/Q-type Ca2+ channels reduced the decrease in glutamate release that was caused by eupafolin, and docking data revealed that eupafolin interacted with P/Q-type Ca2+ channels. Additionally, the inhibition of calcium/calmodulindependent protein kinase II (CaMKII) prevented the effect of eupafolin on evoked glutamate release. Eupafolin also reduced the 4-AP-induced activation of CaMK II and the subsequent phosphorylation of synapsin I, which is the main presynaptic target of CaMKII. Therefore, eupafolin suppresses P/Q-type Ca2+ channels and thereby inhibits CaMKII/synapsin I pathways and the release of glutamate from rat cerebrocortical synaptosomes.
3.The Clinical Observation of Inflammation Theory for Depression:The Initiative of the Formosa Long COVID Multicenter Study (FOCuS)
Shu-Tsen LIU ; Sheng-Che LIN ; Jane Pei-Chen CHANG ; Kai-Jie YANG ; Che-Sheng CHU ; Chia-Chun YANG ; Chih-Sung LIANG ; Ching-Fang SUN ; Shao-Cheng WANG ; Senthil Kumaran SATYANARAYANAN ; Kuan-Pin SU
Clinical Psychopharmacology and Neuroscience 2023;21(1):10-18
There is growing evidence that the coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with increased risks of psychiatric sequelae. Depression, anxiety, cognitive impairments, sleep disturbance, and fatigue during and after the acute phase of COVID-19 are prevalent, long-lasting, and exerting negative consequences on well-being and imposing a huge burden on healthcare systems and society. This current review presented timely updates of clinical research findings, particularly focusing on the pathogenetic mechanisms underlying the neuropsychiatric sequelae, and identified potential key targets for developing effective treatment strategies for long COVID. In addition, we introduced the Formosa Long COVID Multicenter Study (FOCuS), which aims to apply the inflammation theory to the pathogenesis and the psychosocial and nutrition treatments of post-COVID depression and anxiety.