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.
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http://dx.doi.org/10.3390/brainsci11111514 | DOI Listing |
Background: Alzheimer's Disease (AD) is neuropathologically characterized by the accumulation of Amyloid-β (Aβ) plaques, neurofibrillary tangles, and neuroinflammation. GPR3 is a G protein-coupled receptor (GPCR) that has been implicated in Aβ pathogenesis via β-arrestin 2 (βarr2)-mediated intracellular signaling. Genetic deletion of Gpr3 reduces the Aβ plaque burden and cognitive decline in AD transgenic mice.
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Department of Pharmacology, University of the Basque Country UPV/EHU, Leioa, Bizkaia, Spain; Centro de Investigación Biomédica en Red de Salud Mental, Instituto de Salud Carlos III, Spain; Biobizkaia Health Research Institute, Barakaldo, Bizkaia, Spain. Electronic address:
In the rapidly growing field of psychedelic research, psilocybin (and active metabolite psilocin) has been proposed as a promising candidate in the search for novel treatments for neuropsychiatric disorders. Clinical trials have revealed that psilocybin has a large, rapid, and persistent effect in the improvement of symptoms of depression and anxiety. The safety profile is considered favourable, with low toxicity and good tolerance.
View Article and Find Full Text PDFEnviron Sci Technol
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State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China.
Airborne exists widely in the natural environment and is closely related to human health. Growing evidence indicates that environmental air pollution elevates the risk of depressive disorders. However, the potential role of airborne in the development of depression remains unclear.
View Article and Find Full Text PDFInt J Mol Sci
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Department of Psychiatry, Yonsei University Wonju College of Medicine, Wonju 26426, Republic of Korea.
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View Article and Find Full Text PDFBiomedicines
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Guangzhou Key Laboratory of Forensic Multi-Omics for Precision Identification, School of Forensic Medicine, Southern Medical University, Guangzhou 510515, China.
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