P2X7 receptor contributes to long-term neuroinflammation and cognitive impairment in sepsis-surviving mice
Autor(a) principal: | |
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Data de Publicação: | 2023 |
Outros Autores: | , , , , , , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UFRGS |
Texto Completo: | http://hdl.handle.net/10183/261882 |
Resumo: | Introduction: sepsis is defined as a multifactorial debilitating condition with high risks of death. The intense inflammatory response causes deleterious effects on the brain, a condition called sepsis-associated encephalopathy. Neuroinflammation or pathogen recognition are able to stress cells, resulting in ATP (Adenosine Triphosphate) release and P2X7 receptor activation, which is abundantly expressed in the brain. The P2X7 receptor contributes to chronic neurodegenerative and neuroinflammatory diseases; however, its function in long-term neurological impairment caused by sepsis remains unclear. Therefore, we sought to evaluate the effects of P2X7 receptor activation in neuroinflammatory and behavioral changes in sepsis-surviving mice. Methods: sepsis was induced in wild-type (WT), P2X7−/− , and BBG (Brilliant Blue G)-treated mice by cecal ligation and perforation (CLP). On the thirteenth day after the surgery, the cognitive function of mice was assessed using the novel recognition object and Water T-maze tests. Acetylcholinesterase (AChE) activity, microglial and astrocytic activation markers, and cytokine production were also evaluated. Results: Initially, we observed that both WT and P2X7−/− sepsis-surviving mice showed memory impairment 13 days after surgery, once they did not differentiate between novel and familiar objects. Both groups of animals presented increased AChE activity in the hippocampus and cerebral cortex. However, the absence of P2X7 prevented partly this increase in the cerebral cortex. Likewise, P2X7 absence decreased ionized calcium-binding protein 1 (Iba−1 ) and glial fibrillary acidic protein (GFAP) upregulation in the cerebral cortex of sepsis-surviving animals. There was an increase in GFAP protein levels in the cerebral cortex but not in the hippocampus of both WT and P2X7−/− sepsis-surviving animals. Pharmacological inhibition or genetic deletion of P2X7 receptor attenuated the production of Interleukin-1β (IL-1β), Tumor necrosis factor-α (TNF-α), and Interleukin-10 (IL-10). Conclusion: the modulation of the P2X7 receptor in sepsis-surviving animals may reduce neuroinflammation and prevent cognitive impairment due to sepsisassociated encephalopathy, being considered an important therapeutic target. |
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Alves, Vinícius SantosSilva, Joyce Pereira daRodrigues, Fabiana CristinaAraújo, Suzana Maria BernardinoSouza, André Luiz Gouvêa deAguiar, Raíssa Leite TenorioSantos, Stephanie Alexia Cristina SilvaSilva, Milla Souza Pessoa daFerreira, Fernanda SilvaMarques, Eduardo PeilPassos, Beatriz Amanda Barbosa Rangel dosGutierrez, Tatiana MaronKurtenbach, EleonoraCosta, Robson daFigueiredo, Claudia PintoWyse, Angela Terezinha de SouzaSilva, Robson CoutinhoSavio, Luiz Eduardo Baggio2023-07-08T03:36:21Z20231663-9812http://hdl.handle.net/10183/261882001169776Introduction: sepsis is defined as a multifactorial debilitating condition with high risks of death. The intense inflammatory response causes deleterious effects on the brain, a condition called sepsis-associated encephalopathy. Neuroinflammation or pathogen recognition are able to stress cells, resulting in ATP (Adenosine Triphosphate) release and P2X7 receptor activation, which is abundantly expressed in the brain. The P2X7 receptor contributes to chronic neurodegenerative and neuroinflammatory diseases; however, its function in long-term neurological impairment caused by sepsis remains unclear. Therefore, we sought to evaluate the effects of P2X7 receptor activation in neuroinflammatory and behavioral changes in sepsis-surviving mice. Methods: sepsis was induced in wild-type (WT), P2X7−/− , and BBG (Brilliant Blue G)-treated mice by cecal ligation and perforation (CLP). On the thirteenth day after the surgery, the cognitive function of mice was assessed using the novel recognition object and Water T-maze tests. Acetylcholinesterase (AChE) activity, microglial and astrocytic activation markers, and cytokine production were also evaluated. Results: Initially, we observed that both WT and P2X7−/− sepsis-surviving mice showed memory impairment 13 days after surgery, once they did not differentiate between novel and familiar objects. Both groups of animals presented increased AChE activity in the hippocampus and cerebral cortex. However, the absence of P2X7 prevented partly this increase in the cerebral cortex. Likewise, P2X7 absence decreased ionized calcium-binding protein 1 (Iba−1 ) and glial fibrillary acidic protein (GFAP) upregulation in the cerebral cortex of sepsis-surviving animals. There was an increase in GFAP protein levels in the cerebral cortex but not in the hippocampus of both WT and P2X7−/− sepsis-surviving animals. Pharmacological inhibition or genetic deletion of P2X7 receptor attenuated the production of Interleukin-1β (IL-1β), Tumor necrosis factor-α (TNF-α), and Interleukin-10 (IL-10). Conclusion: the modulation of the P2X7 receptor in sepsis-surviving animals may reduce neuroinflammation and prevent cognitive impairment due to sepsisassociated encephalopathy, being considered an important therapeutic target.application/pdfengFrontiers in pharmacology. Lausanne. Vol. 14 (Apr. 2023), 1179723, 13 p.SepseDoenças neuroinflamatóriasDisfunção cognitivaEncefalopatia associada a sepseSepsis-associated encephalopathyP2X7 receptorCognitive impairmentNeuroinflammationBrilliant Blue GAcetylcholinesteraseP2X7 receptor contributes to long-term neuroinflammation and cognitive impairment in sepsis-surviving miceEstrangeiroinfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFRGSinstname:Universidade Federal do Rio Grande do Sul (UFRGS)instacron:UFRGSTEXT001169776.pdf.txt001169776.pdf.txtExtracted Texttext/plain70676http://www.lume.ufrgs.br/bitstream/10183/261882/2/001169776.pdf.txt10f2551f63156bba855abdb71f0f42d1MD52ORIGINAL001169776.pdfTexto completo (inglês)application/pdf1979053http://www.lume.ufrgs.br/bitstream/10183/261882/1/001169776.pdf3c61fff50923b6cc9f1a74ee1b107a3dMD5110183/2618822023-07-09 03:37:12.708633oai:www.lume.ufrgs.br:10183/261882Repositório de PublicaçõesPUBhttps://lume.ufrgs.br/oai/requestopendoar:2023-07-09T06:37:12Repositório Institucional da UFRGS - Universidade Federal do Rio Grande do Sul (UFRGS)false |
dc.title.pt_BR.fl_str_mv |
P2X7 receptor contributes to long-term neuroinflammation and cognitive impairment in sepsis-surviving mice |
title |
P2X7 receptor contributes to long-term neuroinflammation and cognitive impairment in sepsis-surviving mice |
spellingShingle |
P2X7 receptor contributes to long-term neuroinflammation and cognitive impairment in sepsis-surviving mice Alves, Vinícius Santos Sepse Doenças neuroinflamatórias Disfunção cognitiva Encefalopatia associada a sepse Sepsis-associated encephalopathy P2X7 receptor Cognitive impairment Neuroinflammation Brilliant Blue G Acetylcholinesterase |
title_short |
P2X7 receptor contributes to long-term neuroinflammation and cognitive impairment in sepsis-surviving mice |
title_full |
P2X7 receptor contributes to long-term neuroinflammation and cognitive impairment in sepsis-surviving mice |
title_fullStr |
P2X7 receptor contributes to long-term neuroinflammation and cognitive impairment in sepsis-surviving mice |
title_full_unstemmed |
P2X7 receptor contributes to long-term neuroinflammation and cognitive impairment in sepsis-surviving mice |
title_sort |
P2X7 receptor contributes to long-term neuroinflammation and cognitive impairment in sepsis-surviving mice |
author |
Alves, Vinícius Santos |
author_facet |
Alves, Vinícius Santos Silva, Joyce Pereira da Rodrigues, Fabiana Cristina Araújo, Suzana Maria Bernardino Souza, André Luiz Gouvêa de Aguiar, Raíssa Leite Tenorio Santos, Stephanie Alexia Cristina Silva Silva, Milla Souza Pessoa da Ferreira, Fernanda Silva Marques, Eduardo Peil Passos, Beatriz Amanda Barbosa Rangel dos Gutierrez, Tatiana Maron Kurtenbach, Eleonora Costa, Robson da Figueiredo, Claudia Pinto Wyse, Angela Terezinha de Souza Silva, Robson Coutinho Savio, Luiz Eduardo Baggio |
author_role |
author |
author2 |
Silva, Joyce Pereira da Rodrigues, Fabiana Cristina Araújo, Suzana Maria Bernardino Souza, André Luiz Gouvêa de Aguiar, Raíssa Leite Tenorio Santos, Stephanie Alexia Cristina Silva Silva, Milla Souza Pessoa da Ferreira, Fernanda Silva Marques, Eduardo Peil Passos, Beatriz Amanda Barbosa Rangel dos Gutierrez, Tatiana Maron Kurtenbach, Eleonora Costa, Robson da Figueiredo, Claudia Pinto Wyse, Angela Terezinha de Souza Silva, Robson Coutinho Savio, Luiz Eduardo Baggio |
author2_role |
author author author author author author author author author author author author author author author author author |
dc.contributor.author.fl_str_mv |
Alves, Vinícius Santos Silva, Joyce Pereira da Rodrigues, Fabiana Cristina Araújo, Suzana Maria Bernardino Souza, André Luiz Gouvêa de Aguiar, Raíssa Leite Tenorio Santos, Stephanie Alexia Cristina Silva Silva, Milla Souza Pessoa da Ferreira, Fernanda Silva Marques, Eduardo Peil Passos, Beatriz Amanda Barbosa Rangel dos Gutierrez, Tatiana Maron Kurtenbach, Eleonora Costa, Robson da Figueiredo, Claudia Pinto Wyse, Angela Terezinha de Souza Silva, Robson Coutinho Savio, Luiz Eduardo Baggio |
dc.subject.por.fl_str_mv |
Sepse Doenças neuroinflamatórias Disfunção cognitiva Encefalopatia associada a sepse |
topic |
Sepse Doenças neuroinflamatórias Disfunção cognitiva Encefalopatia associada a sepse Sepsis-associated encephalopathy P2X7 receptor Cognitive impairment Neuroinflammation Brilliant Blue G Acetylcholinesterase |
dc.subject.eng.fl_str_mv |
Sepsis-associated encephalopathy P2X7 receptor Cognitive impairment Neuroinflammation Brilliant Blue G Acetylcholinesterase |
description |
Introduction: sepsis is defined as a multifactorial debilitating condition with high risks of death. The intense inflammatory response causes deleterious effects on the brain, a condition called sepsis-associated encephalopathy. Neuroinflammation or pathogen recognition are able to stress cells, resulting in ATP (Adenosine Triphosphate) release and P2X7 receptor activation, which is abundantly expressed in the brain. The P2X7 receptor contributes to chronic neurodegenerative and neuroinflammatory diseases; however, its function in long-term neurological impairment caused by sepsis remains unclear. Therefore, we sought to evaluate the effects of P2X7 receptor activation in neuroinflammatory and behavioral changes in sepsis-surviving mice. Methods: sepsis was induced in wild-type (WT), P2X7−/− , and BBG (Brilliant Blue G)-treated mice by cecal ligation and perforation (CLP). On the thirteenth day after the surgery, the cognitive function of mice was assessed using the novel recognition object and Water T-maze tests. Acetylcholinesterase (AChE) activity, microglial and astrocytic activation markers, and cytokine production were also evaluated. Results: Initially, we observed that both WT and P2X7−/− sepsis-surviving mice showed memory impairment 13 days after surgery, once they did not differentiate between novel and familiar objects. Both groups of animals presented increased AChE activity in the hippocampus and cerebral cortex. However, the absence of P2X7 prevented partly this increase in the cerebral cortex. Likewise, P2X7 absence decreased ionized calcium-binding protein 1 (Iba−1 ) and glial fibrillary acidic protein (GFAP) upregulation in the cerebral cortex of sepsis-surviving animals. There was an increase in GFAP protein levels in the cerebral cortex but not in the hippocampus of both WT and P2X7−/− sepsis-surviving animals. Pharmacological inhibition or genetic deletion of P2X7 receptor attenuated the production of Interleukin-1β (IL-1β), Tumor necrosis factor-α (TNF-α), and Interleukin-10 (IL-10). Conclusion: the modulation of the P2X7 receptor in sepsis-surviving animals may reduce neuroinflammation and prevent cognitive impairment due to sepsisassociated encephalopathy, being considered an important therapeutic target. |
publishDate |
2023 |
dc.date.accessioned.fl_str_mv |
2023-07-08T03:36:21Z |
dc.date.issued.fl_str_mv |
2023 |
dc.type.driver.fl_str_mv |
Estrangeiro info:eu-repo/semantics/article |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10183/261882 |
dc.identifier.issn.pt_BR.fl_str_mv |
1663-9812 |
dc.identifier.nrb.pt_BR.fl_str_mv |
001169776 |
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1663-9812 001169776 |
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http://hdl.handle.net/10183/261882 |
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eng |
language |
eng |
dc.relation.ispartof.pt_BR.fl_str_mv |
Frontiers in pharmacology. Lausanne. Vol. 14 (Apr. 2023), 1179723, 13 p. |
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