Ganoderic Acid A-Mediated Modulation of Microglial Polarization is Involved in Depressive-Like Behaviors and Neuroinflammation in a Rat Model of Post-Stroke Depression

Ling Zhang,1 Lei Zhang,2 Rubo Sui1 1Department of Neurology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, People’s Republic of China; 2College of Nursing, Jinzhou Medical University, Jinzhou, People’s Republic of ChinaCorrespondence: Lei ZhangCollege of Nursing, Jinzhou Medi...

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Autores principales:	Zhang L, Sui R
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2021
Materias:	ganoderic acid a post-stroke depression neuronal damage inflammation microglial polarization extracellular signal-regulated kinase Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429
Acceso en línea:	https://doaj.org/article/a50215896b414f5fa02f292833347da3
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spelling	oai:doaj.org-article:a50215896b414f5fa02f292833347da32021-12-02T19:06:36ZGanoderic Acid A-Mediated Modulation of Microglial Polarization is Involved in Depressive-Like Behaviors and Neuroinflammation in a Rat Model of Post-Stroke Depression1178-2021https://doaj.org/article/a50215896b414f5fa02f292833347da32021-08-01T00:00:00Zhttps://www.dovepress.com/ganoderic-acid-a-mediated-modulation-of-microglial-polarization-is-inv-peer-reviewed-fulltext-article-NDThttps://doaj.org/toc/1178-2021Ling Zhang,1 Lei Zhang,2 Rubo Sui1 1Department of Neurology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, People’s Republic of China; 2College of Nursing, Jinzhou Medical University, Jinzhou, People’s Republic of ChinaCorrespondence: Lei ZhangCollege of Nursing, Jinzhou Medical University, No. 40, Section 3, Songpo Road, Guta District, Jinzhou, 121001, Liaoning Province, People’s Republic of ChinaEmail zhanglei7812713@163.comBackground: Post-stroke depression (PSD) is a common complication after stroke. Ganoderic acid A (GAA), one of the main bioactive Ganoderma triterpenoids, exerts preventive and therapeutic effects in many diseases. However, the function of GAA in PSD has not been well studied.Methods: PSD model was established via stimulating rats with chronic unpredictable mild stress stimulations (CUMS) after middle cerebral artery occlusion (MCAO). Rats were treated with GAA before CUMS. Depressive-like behaviors were investigated by body weight alteration, open field test (OFT), and sucrose preference test (SPT). Neuronal damage was evaluated by hematoxylin and eosin (HE) staining and Western blotting. Inflammation was detected by enzyme-linked immunosorbent assay (ELISA) and quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Microglial polarization was analyzed via qRT-PCR and Western blotting. The extracellular signal-regulated kinase (ERK)/cAMP-response element-binding protein (CREB) pathway was analyzed by Western blotting, and inactivated by the inhibitor PD98059 (PD).Results: GAA attenuated PSD-induced depressive-like behaviors in rats. GAA mitigated PSD-induced neuronal damage and reduced BDNF and NGF levels in the cerebral hippocampus. GAA weakened PSD-induced inflammatory response in the cerebral hippocampus. GAA prevented pro-inflammatory (M1) polarization and promoted anti-inflammatory (M2) polarization, as indicated by decreased iNOS and CD86 levels and increased Arg-1 and CD206 levels. GAA restored the PSD-induced inactivation of the ERK/CREB pathway. GAA regulated M1/M2 microglial polarization by activating the ERK/CREB pathway.Conclusion: GAA alleviated the depressive-like behaviors and brain inflammation in PSD rats, indicating its potential for PSD therapy.Keywords: ganoderic acid A, post-stroke depression, neuronal damage, inflammation, microglial polarization, extracellular signal-regulated kinaseZhang LZhang LSui RDove Medical Pressarticleganoderic acid apost-stroke depressionneuronal damageinflammationmicroglial polarizationextracellular signal-regulated kinaseNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571Neurology. Diseases of the nervous systemRC346-429ENNeuropsychiatric Disease and Treatment, Vol Volume 17, Pp 2671-2681 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	ganoderic acid a post-stroke depression neuronal damage inflammation microglial polarization extracellular signal-regulated kinase Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429
spellingShingle	ganoderic acid a post-stroke depression neuronal damage inflammation microglial polarization extracellular signal-regulated kinase Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429 Zhang L Zhang L Sui R Ganoderic Acid A-Mediated Modulation of Microglial Polarization is Involved in Depressive-Like Behaviors and Neuroinflammation in a Rat Model of Post-Stroke Depression
description	Ling Zhang,1 Lei Zhang,2 Rubo Sui1 1Department of Neurology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, People’s Republic of China; 2College of Nursing, Jinzhou Medical University, Jinzhou, People’s Republic of ChinaCorrespondence: Lei ZhangCollege of Nursing, Jinzhou Medical University, No. 40, Section 3, Songpo Road, Guta District, Jinzhou, 121001, Liaoning Province, People’s Republic of ChinaEmail zhanglei7812713@163.comBackground: Post-stroke depression (PSD) is a common complication after stroke. Ganoderic acid A (GAA), one of the main bioactive Ganoderma triterpenoids, exerts preventive and therapeutic effects in many diseases. However, the function of GAA in PSD has not been well studied.Methods: PSD model was established via stimulating rats with chronic unpredictable mild stress stimulations (CUMS) after middle cerebral artery occlusion (MCAO). Rats were treated with GAA before CUMS. Depressive-like behaviors were investigated by body weight alteration, open field test (OFT), and sucrose preference test (SPT). Neuronal damage was evaluated by hematoxylin and eosin (HE) staining and Western blotting. Inflammation was detected by enzyme-linked immunosorbent assay (ELISA) and quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Microglial polarization was analyzed via qRT-PCR and Western blotting. The extracellular signal-regulated kinase (ERK)/cAMP-response element-binding protein (CREB) pathway was analyzed by Western blotting, and inactivated by the inhibitor PD98059 (PD).Results: GAA attenuated PSD-induced depressive-like behaviors in rats. GAA mitigated PSD-induced neuronal damage and reduced BDNF and NGF levels in the cerebral hippocampus. GAA weakened PSD-induced inflammatory response in the cerebral hippocampus. GAA prevented pro-inflammatory (M1) polarization and promoted anti-inflammatory (M2) polarization, as indicated by decreased iNOS and CD86 levels and increased Arg-1 and CD206 levels. GAA restored the PSD-induced inactivation of the ERK/CREB pathway. GAA regulated M1/M2 microglial polarization by activating the ERK/CREB pathway.Conclusion: GAA alleviated the depressive-like behaviors and brain inflammation in PSD rats, indicating its potential for PSD therapy.Keywords: ganoderic acid A, post-stroke depression, neuronal damage, inflammation, microglial polarization, extracellular signal-regulated kinase
format	article
author	Zhang L Zhang L Sui R
author_facet	Zhang L Zhang L Sui R
author_sort	Zhang L
title	Ganoderic Acid A-Mediated Modulation of Microglial Polarization is Involved in Depressive-Like Behaviors and Neuroinflammation in a Rat Model of Post-Stroke Depression
title_short	Ganoderic Acid A-Mediated Modulation of Microglial Polarization is Involved in Depressive-Like Behaviors and Neuroinflammation in a Rat Model of Post-Stroke Depression
title_full	Ganoderic Acid A-Mediated Modulation of Microglial Polarization is Involved in Depressive-Like Behaviors and Neuroinflammation in a Rat Model of Post-Stroke Depression
title_fullStr	Ganoderic Acid A-Mediated Modulation of Microglial Polarization is Involved in Depressive-Like Behaviors and Neuroinflammation in a Rat Model of Post-Stroke Depression
title_full_unstemmed	Ganoderic Acid A-Mediated Modulation of Microglial Polarization is Involved in Depressive-Like Behaviors and Neuroinflammation in a Rat Model of Post-Stroke Depression
title_sort	ganoderic acid a-mediated modulation of microglial polarization is involved in depressive-like behaviors and neuroinflammation in a rat model of post-stroke depression
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/a50215896b414f5fa02f292833347da3
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Ganoderic Acid A-Mediated Modulation of Microglial Polarization is Involved in Depressive-Like Behaviors and Neuroinflammation in a Rat Model of Post-Stroke Depression

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