Chlorogenic Acid Decreases Glutamate Release from Rat Cortical Nerve Terminals by P/Q-Type Ca<sup>2+</sup> Channel Suppression: A Possible Neuroprotective Mechanism

The glutamatergic neurotransmitter system has received substantial attention in research on the pathophysiology and treatment of neurological disorders. The study investigated the effect of the polyphenolic compound chlorogenic acid (CGA) on glutamate release in rat cerebrocortical nerve terminals (...

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Autores principales:	Yi-Chieh Hung, Yi-Hsiu Kuo, Pei-Wen Hsieh, Ting-Yang Hsieh, Jinn-Rung Kuo, Su-Jane Wang
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	chlorogenic acid glutamate release P/Q-type Ca<sup>2+</sup> channel CaMKII neuroprotection cerebral cortex Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/d0487f8944dc40f2958e1e6fde8450ae
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spelling	oai:doaj.org-article:d0487f8944dc40f2958e1e6fde8450ae2021-11-11T16:54:33ZChlorogenic Acid Decreases Glutamate Release from Rat Cortical Nerve Terminals by P/Q-Type Ca<sup>2+</sup> Channel Suppression: A Possible Neuroprotective Mechanism10.3390/ijms2221114471422-00671661-6596https://doaj.org/article/d0487f8944dc40f2958e1e6fde8450ae2021-10-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11447https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067The glutamatergic neurotransmitter system has received substantial attention in research on the pathophysiology and treatment of neurological disorders. The study investigated the effect of the polyphenolic compound chlorogenic acid (CGA) on glutamate release in rat cerebrocortical nerve terminals (synaptosomes). CGA inhibited 4-aminopyridine (4-AP)-induced glutamate release from synaptosomes. This inhibition was prevented in the absence of extracellular Ca<sup>2+</sup> and was associated with the inhibition of 4-AP-induced elevation of Ca<sup>2+</sup> but was not attributed to changes in synaptosomal membrane potential. In line with evidence observed through molecular docking, CGA did not inhibit glutamate release in the presence of P/Q-type Ca<sup>2+</sup> channel inhibitors; therefore, CGA-induced inhibition of glutamate release may be mediated by P/Q-type Ca<sup>2+</sup> channels. CGA-induced inhibition of glutamate release was also diminished by the calmodulin and Ca<sup>2+</sup>/calmodilin-dependent kinase II (CaMKII) inhibitors, and CGA reduced the phosphorylation of CaMKII and its substrate, synapsin I. Furthermore, pretreatment with intraperitoneal CGA injection attenuated the glutamate increment and neuronal damage in the rat cortex that were induced by kainic acid administration. These results indicate that CGA inhibits glutamate release from cortical synaptosomes by suppressing P/Q-type Ca<sup>2+</sup> channels and CaMKII/synapsin I pathways, thereby preventing excitotoxic damage to cortical neurons.Yi-Chieh HungYi-Hsiu KuoPei-Wen HsiehTing-Yang HsiehJinn-Rung KuoSu-Jane WangMDPI AGarticlechlorogenic acidglutamate releaseP/Q-type Ca<sup>2+</sup> channelCaMKIIneuroprotectioncerebral cortexBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11447, p 11447 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	chlorogenic acid glutamate release P/Q-type Ca<sup>2+</sup> channel CaMKII neuroprotection cerebral cortex Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	chlorogenic acid glutamate release P/Q-type Ca<sup>2+</sup> channel CaMKII neuroprotection cerebral cortex Biology (General) QH301-705.5 Chemistry QD1-999 Yi-Chieh Hung Yi-Hsiu Kuo Pei-Wen Hsieh Ting-Yang Hsieh Jinn-Rung Kuo Su-Jane Wang Chlorogenic Acid Decreases Glutamate Release from Rat Cortical Nerve Terminals by P/Q-Type Ca<sup>2+</sup> Channel Suppression: A Possible Neuroprotective Mechanism
description	The glutamatergic neurotransmitter system has received substantial attention in research on the pathophysiology and treatment of neurological disorders. The study investigated the effect of the polyphenolic compound chlorogenic acid (CGA) on glutamate release in rat cerebrocortical nerve terminals (synaptosomes). CGA inhibited 4-aminopyridine (4-AP)-induced glutamate release from synaptosomes. This inhibition was prevented in the absence of extracellular Ca<sup>2+</sup> and was associated with the inhibition of 4-AP-induced elevation of Ca<sup>2+</sup> but was not attributed to changes in synaptosomal membrane potential. In line with evidence observed through molecular docking, CGA did not inhibit glutamate release in the presence of P/Q-type Ca<sup>2+</sup> channel inhibitors; therefore, CGA-induced inhibition of glutamate release may be mediated by P/Q-type Ca<sup>2+</sup> channels. CGA-induced inhibition of glutamate release was also diminished by the calmodulin and Ca<sup>2+</sup>/calmodilin-dependent kinase II (CaMKII) inhibitors, and CGA reduced the phosphorylation of CaMKII and its substrate, synapsin I. Furthermore, pretreatment with intraperitoneal CGA injection attenuated the glutamate increment and neuronal damage in the rat cortex that were induced by kainic acid administration. These results indicate that CGA inhibits glutamate release from cortical synaptosomes by suppressing P/Q-type Ca<sup>2+</sup> channels and CaMKII/synapsin I pathways, thereby preventing excitotoxic damage to cortical neurons.
format	article
author	Yi-Chieh Hung Yi-Hsiu Kuo Pei-Wen Hsieh Ting-Yang Hsieh Jinn-Rung Kuo Su-Jane Wang
author_facet	Yi-Chieh Hung Yi-Hsiu Kuo Pei-Wen Hsieh Ting-Yang Hsieh Jinn-Rung Kuo Su-Jane Wang
author_sort	Yi-Chieh Hung
title	Chlorogenic Acid Decreases Glutamate Release from Rat Cortical Nerve Terminals by P/Q-Type Ca<sup>2+</sup> Channel Suppression: A Possible Neuroprotective Mechanism
title_short	Chlorogenic Acid Decreases Glutamate Release from Rat Cortical Nerve Terminals by P/Q-Type Ca<sup>2+</sup> Channel Suppression: A Possible Neuroprotective Mechanism
title_full	Chlorogenic Acid Decreases Glutamate Release from Rat Cortical Nerve Terminals by P/Q-Type Ca<sup>2+</sup> Channel Suppression: A Possible Neuroprotective Mechanism
title_fullStr	Chlorogenic Acid Decreases Glutamate Release from Rat Cortical Nerve Terminals by P/Q-Type Ca<sup>2+</sup> Channel Suppression: A Possible Neuroprotective Mechanism
title_full_unstemmed	Chlorogenic Acid Decreases Glutamate Release from Rat Cortical Nerve Terminals by P/Q-Type Ca<sup>2+</sup> Channel Suppression: A Possible Neuroprotective Mechanism
title_sort	chlorogenic acid decreases glutamate release from rat cortical nerve terminals by p/q-type ca<sup>2+</sup> channel suppression: a possible neuroprotective mechanism
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/d0487f8944dc40f2958e1e6fde8450ae
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Chlorogenic Acid Decreases Glutamate Release from Rat Cortical Nerve Terminals by P/Q-Type Ca<sup>2+</sup> Channel Suppression: A Possible Neuroprotective Mechanism

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