The Role of Neutrophil Extracellular Traps in Lipopolysaccharide-Induced Depression-like Behaviors in Mice

Peripheral inflammation plays a key role in the development of depression-like behaviors. However, the mechanisms underlying these effects remain largely unknown. Here, we found that the level of citrullinated histone H3 (cit-H3) significantly increased in the plasma of wildtype mice treated with li...

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Autores principales:	Yue Kong, Guiqin He, Xiaolin Zhang, Jin Li
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	neutrophil extracellular traps inflammation depression-like behavior microglia Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
Acceso en línea:	https://doaj.org/article/6253bcc658bf4396a5a5ef05e536fc8d
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spelling	oai:doaj.org-article:6253bcc658bf4396a5a5ef05e536fc8d2021-11-25T16:58:49ZThe Role of Neutrophil Extracellular Traps in Lipopolysaccharide-Induced Depression-like Behaviors in Mice10.3390/brainsci111115142076-3425https://doaj.org/article/6253bcc658bf4396a5a5ef05e536fc8d2021-11-01T00:00:00Zhttps://www.mdpi.com/2076-3425/11/11/1514https://doaj.org/toc/2076-3425Peripheral inflammation plays a key role in the development of depression-like behaviors. However, the mechanisms underlying these effects remain largely unknown. Here, we found that the level of citrullinated histone H3 (cit-H3) significantly increased in the plasma of wildtype mice treated with lipopolysaccharide (LPS), which indicated that neutrophil extracellular traps (NETs) were formed. Moreover, the LPS-induced depression-like and asocial behaviors were significantly alleviated in the mice deficient of NETs. Mechanistically, NETs formation aggravated peripheral inflammation by increasing the concentrations of TNF-α, IL-1β and IL-6 in plasma, which are major proinflammatory cytokines that can enter the brain, resulting in microglia activation and reduced astrocytes. Following this, increased TNF-α and IL-1β were released into brain, inducing neuroinflammation and finally depression-like behaviors. Prohibiting NETs by PAD4 ablation significantly prevented LPS-induced microglia activation and the loss of astrocytes. Our results propose the role for peripheral NETs in LPS-induced depression-like behavior, and that NETs might be a potential target to prevent inflammation-induced major depressive disorder.Yue KongGuiqin HeXiaolin ZhangJin LiMDPI AGarticleneutrophil extracellular trapsinflammationdepression-like behaviormicrogliaNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571ENBrain Sciences, Vol 11, Iss 1514, p 1514 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	neutrophil extracellular traps inflammation depression-like behavior microglia Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
spellingShingle	neutrophil extracellular traps inflammation depression-like behavior microglia Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Yue Kong Guiqin He Xiaolin Zhang Jin Li The Role of Neutrophil Extracellular Traps in Lipopolysaccharide-Induced Depression-like Behaviors in Mice
description	Peripheral inflammation plays a key role in the development of depression-like behaviors. However, the mechanisms underlying these effects remain largely unknown. Here, we found that the level of citrullinated histone H3 (cit-H3) significantly increased in the plasma of wildtype mice treated with lipopolysaccharide (LPS), which indicated that neutrophil extracellular traps (NETs) were formed. Moreover, the LPS-induced depression-like and asocial behaviors were significantly alleviated in the mice deficient of NETs. Mechanistically, NETs formation aggravated peripheral inflammation by increasing the concentrations of TNF-α, IL-1β and IL-6 in plasma, which are major proinflammatory cytokines that can enter the brain, resulting in microglia activation and reduced astrocytes. Following this, increased TNF-α and IL-1β were released into brain, inducing neuroinflammation and finally depression-like behaviors. Prohibiting NETs by PAD4 ablation significantly prevented LPS-induced microglia activation and the loss of astrocytes. Our results propose the role for peripheral NETs in LPS-induced depression-like behavior, and that NETs might be a potential target to prevent inflammation-induced major depressive disorder.
format	article
author	Yue Kong Guiqin He Xiaolin Zhang Jin Li
author_facet	Yue Kong Guiqin He Xiaolin Zhang Jin Li
author_sort	Yue Kong
title	The Role of Neutrophil Extracellular Traps in Lipopolysaccharide-Induced Depression-like Behaviors in Mice
title_short	The Role of Neutrophil Extracellular Traps in Lipopolysaccharide-Induced Depression-like Behaviors in Mice
title_full	The Role of Neutrophil Extracellular Traps in Lipopolysaccharide-Induced Depression-like Behaviors in Mice
title_fullStr	The Role of Neutrophil Extracellular Traps in Lipopolysaccharide-Induced Depression-like Behaviors in Mice
title_full_unstemmed	The Role of Neutrophil Extracellular Traps in Lipopolysaccharide-Induced Depression-like Behaviors in Mice
title_sort	role of neutrophil extracellular traps in lipopolysaccharide-induced depression-like behaviors in mice
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/6253bcc658bf4396a5a5ef05e536fc8d
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The Role of Neutrophil Extracellular Traps in Lipopolysaccharide-Induced Depression-like Behaviors in Mice

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