Astaxanthin Attenuates Neuroinflammation in Status Epilepticus Rats by Regulating the ATP-P2X7R Signal
Ming Wang,1,2 Xiaolin Deng,1,2 Yangmei Xie,1,2 Yinghui Chen1,2 1Department of Neurology, Jinshan Hospital, Fudan University, Shanghai, People’s Republic of China; 2Department of Neurology, Huashan Hospital North, Fudan University, Shanghai, People’s Republic of ChinaCorrespondenc...
Main Authors: | , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Dove Medical Press
2020-04-01
|
Series: | Drug Design, Development and Therapy |
Subjects: | |
Online Access: | https://www.dovepress.com/astaxanthin-attenuates-neuroinflammation-in-status-epilepticus-rats-by-peer-reviewed-article-DDDT |
id |
doaj-102b367700cd4d9e8539a7c00fc58f91 |
---|---|
record_format |
Article |
spelling |
doaj-102b367700cd4d9e8539a7c00fc58f912020-11-25T02:54:36ZengDove Medical PressDrug Design, Development and Therapy1177-88812020-04-01Volume 141651166253437Astaxanthin Attenuates Neuroinflammation in Status Epilepticus Rats by Regulating the ATP-P2X7R SignalWang MDeng XXie YChen YMing Wang,1,2 Xiaolin Deng,1,2 Yangmei Xie,1,2 Yinghui Chen1,2 1Department of Neurology, Jinshan Hospital, Fudan University, Shanghai, People’s Republic of China; 2Department of Neurology, Huashan Hospital North, Fudan University, Shanghai, People’s Republic of ChinaCorrespondence: Yinghui ChenDepartment of Neurology, Huashan Hospital North, Fudan University, Shanghai, People’s Republic of ChinaTel +86 18930819605Email yinghuichen@fudan.edu.cnBackground: As a life-threatening neurological emergency, status epilepticus (SE) is often refractory to available treatment. Current studies have shown a causal role of neuroinflammation in patients with lower seizure thresholds and driving seizures. The ATP-gated purinergic P2X7 receptor (P2X7R) is mainly expressed on the microglia, which function as gatekeepers of inflammation. Although emerging evidence has demonstrated significant anti-inflammatory effects of astaxanthin (AST) in SE, the associated mechanism remains unclear. Therefore, this study aimed to clarify the effects of AST on P2X7R-related inflammation in SE.Methods: SE was induced in rats using lithium–pilocarpine, and AST was administered 1 h after SE induction. Rat microglia were treated with lipopolysaccharide (LPS), AST, ATP, 2,3-O-4-benzoyl-4-benzoyl-ATP (BzATP) and oxidized ATP (oxATP). The Morris water maze, immunohistochemistry, and Nissl staining were performed in rats. Expressions of P2X7R and inflammatory cytokines (such as cycloxygenase-2 (Cox-2), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α)) were detected using real-time polymerase chain reaction (RT-PCR) and Western blot (WB) both in rats and microglia. ATP concentration in the microglia was evaluated using ELISA.Results: The AST alleviated hippocampal injury and improved cognitive dysfunction induced by SE. AST also effectively inhibited inflammation and downregulated P2X7R expression in both rat brain and microglia. The results also showed that AST reduced the extracellular ATP levels and that P2X7R expression could be increased by extracellular ATP. In addition, BzATP upregulates the expression of P2X7R and inflammatory factors in microglia. Conversely, it downregulates the expression of P2X7R and inflammatory factors.Conclusion: Our study suggests that AST attenuated ATP-P2X7R mediated inflammation in SE.Keywords: status epilepticus, astaxanthin, neuroinflammation, P2X7R, ATPhttps://www.dovepress.com/astaxanthin-attenuates-neuroinflammation-in-status-epilepticus-rats-by-peer-reviewed-article-DDDTstatus epilepticus1astaxanthin2neuroinflammation3p2x7r4atp5. |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Wang M Deng X Xie Y Chen Y |
spellingShingle |
Wang M Deng X Xie Y Chen Y Astaxanthin Attenuates Neuroinflammation in Status Epilepticus Rats by Regulating the ATP-P2X7R Signal Drug Design, Development and Therapy status epilepticus1 astaxanthin2 neuroinflammation3 p2x7r4 atp5. |
author_facet |
Wang M Deng X Xie Y Chen Y |
author_sort |
Wang M |
title |
Astaxanthin Attenuates Neuroinflammation in Status Epilepticus Rats by Regulating the ATP-P2X7R Signal |
title_short |
Astaxanthin Attenuates Neuroinflammation in Status Epilepticus Rats by Regulating the ATP-P2X7R Signal |
title_full |
Astaxanthin Attenuates Neuroinflammation in Status Epilepticus Rats by Regulating the ATP-P2X7R Signal |
title_fullStr |
Astaxanthin Attenuates Neuroinflammation in Status Epilepticus Rats by Regulating the ATP-P2X7R Signal |
title_full_unstemmed |
Astaxanthin Attenuates Neuroinflammation in Status Epilepticus Rats by Regulating the ATP-P2X7R Signal |
title_sort |
astaxanthin attenuates neuroinflammation in status epilepticus rats by regulating the atp-p2x7r signal |
publisher |
Dove Medical Press |
series |
Drug Design, Development and Therapy |
issn |
1177-8881 |
publishDate |
2020-04-01 |
description |
Ming Wang,1,2 Xiaolin Deng,1,2 Yangmei Xie,1,2 Yinghui Chen1,2 1Department of Neurology, Jinshan Hospital, Fudan University, Shanghai, People’s Republic of China; 2Department of Neurology, Huashan Hospital North, Fudan University, Shanghai, People’s Republic of ChinaCorrespondence: Yinghui ChenDepartment of Neurology, Huashan Hospital North, Fudan University, Shanghai, People’s Republic of ChinaTel +86 18930819605Email yinghuichen@fudan.edu.cnBackground: As a life-threatening neurological emergency, status epilepticus (SE) is often refractory to available treatment. Current studies have shown a causal role of neuroinflammation in patients with lower seizure thresholds and driving seizures. The ATP-gated purinergic P2X7 receptor (P2X7R) is mainly expressed on the microglia, which function as gatekeepers of inflammation. Although emerging evidence has demonstrated significant anti-inflammatory effects of astaxanthin (AST) in SE, the associated mechanism remains unclear. Therefore, this study aimed to clarify the effects of AST on P2X7R-related inflammation in SE.Methods: SE was induced in rats using lithium–pilocarpine, and AST was administered 1 h after SE induction. Rat microglia were treated with lipopolysaccharide (LPS), AST, ATP, 2,3-O-4-benzoyl-4-benzoyl-ATP (BzATP) and oxidized ATP (oxATP). The Morris water maze, immunohistochemistry, and Nissl staining were performed in rats. Expressions of P2X7R and inflammatory cytokines (such as cycloxygenase-2 (Cox-2), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α)) were detected using real-time polymerase chain reaction (RT-PCR) and Western blot (WB) both in rats and microglia. ATP concentration in the microglia was evaluated using ELISA.Results: The AST alleviated hippocampal injury and improved cognitive dysfunction induced by SE. AST also effectively inhibited inflammation and downregulated P2X7R expression in both rat brain and microglia. The results also showed that AST reduced the extracellular ATP levels and that P2X7R expression could be increased by extracellular ATP. In addition, BzATP upregulates the expression of P2X7R and inflammatory factors in microglia. Conversely, it downregulates the expression of P2X7R and inflammatory factors.Conclusion: Our study suggests that AST attenuated ATP-P2X7R mediated inflammation in SE.Keywords: status epilepticus, astaxanthin, neuroinflammation, P2X7R, ATP |
topic |
status epilepticus1 astaxanthin2 neuroinflammation3 p2x7r4 atp5. |
url |
https://www.dovepress.com/astaxanthin-attenuates-neuroinflammation-in-status-epilepticus-rats-by-peer-reviewed-article-DDDT |
work_keys_str_mv |
AT wangm astaxanthinattenuatesneuroinflammationinstatusepilepticusratsbyregulatingtheatpp2x7rsignal AT dengx astaxanthinattenuatesneuroinflammationinstatusepilepticusratsbyregulatingtheatpp2x7rsignal AT xiey astaxanthinattenuatesneuroinflammationinstatusepilepticusratsbyregulatingtheatpp2x7rsignal AT cheny astaxanthinattenuatesneuroinflammationinstatusepilepticusratsbyregulatingtheatpp2x7rsignal |
_version_ |
1724720084238204928 |