Polysaccharides from Ganoderma lucidum attenuate microglia-mediated neuroinflammation and modulate microglial phagocytosis and behavioural response

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Abstract

Background

Ganoderma lucidum (GL) has been widely used in Asian countries for hundreds of years to promote health and longevity. The pharmacological functions of which had been classified, including the activation of innate immune responses, suppression of tumour and modulation of cell proliferations. Effective fractions of Ganoderma lucidum polysaccharides (GLP) had already been reported to regulate the immune system. Nevertheless, the role of GLP in the microglia-mediated neuroinflammation has not been sufficiently elucidated. Further, GLP effect on microglial behavioural modulations in correlation with the inflammatory responses remains to be unravelled. The aim of this work was to quantitatively analyse the contributions of GLP on microglia.

Methods

The BV2 microglia and primary mouse microglia were stimulated by lipopolysaccharides (LPS) and amyloid beta ₄₂ (Aβ ₄₂) oligomer, respectively. Investigation on the effect of GLP was carried by quantitative determination of the microglial pro- and anti-inflammatory cytokine expressions and behavioural modulations including migration, morphology and phagocytosis. Analysis of microglial morphology and phagocytosis modulations was confirmed in the zebrafish brain.

Results

Quantitative results revealed that GLP down-regulates LPS- or Aβ-induced pro-inflammatory cytokines and promotes anti-inflammatory cytokine expressions in BV-2 and primary microglia. In addition, GLP attenuates inflammation-related microglial migration, morphological alterations and phagocytosis probabilities. We also showed that modulations of microglial behavioural responses were associated with MCP-1 and C1q expressions.

Conclusions

Overall, our study provides an insight into the GLP regulation of LPS- and Aβ-induced neuroinflammation and serves an implication that the neuroprotective function of GLP might be achieved through modulation of microglial inflammatory and behavioural responses.

Electronic supplementary material

The online version of this article (doi:10.1186/s12974-017-0839-0) contains supplementary material, which is available to authorized users.

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Most cited references 38

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Reciprocal regulation between resting microglial dynamics and neuronal activity in vivo.

Ying Li, Xu-Fei Du, Chang-Sheng Liu … (2012)

Microglia are the primary immune cells in the brain. Under physiological conditions, they typically stay in a "resting" state, with ramified processes continuously extending to and retracting from surrounding neural tissues. Whether and how such highly dynamic resting microglia functionally interact with surrounding neurons are still unclear. Using in vivo time-lapse imaging of both microglial morphology and neuronal activity in the optic tectum of larval zebrafish, we found that neuronal activity steers resting microglial processes and facilitates their contact with highly active neurons. This process requires the activation of pannexin-1 hemichannels on neurons. Reciprocally, such resting microglia-neuron contact reduces both spontaneous and visually evoked activities of contacted neurons. Our findings reveal an instructive role for neuronal activity in resting microglial motility and suggest the function for microglia in homeostatic regulation of neuronal activity in the healthy brain. Copyright © 2012 Elsevier Inc. All rights reserved.

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Chemokines and disease.

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We examine here several diseases that are associated with inappropriate activation of the chemokine network. Detailed comment has been restricted to pathological states for which there are compelling data either from clinical observations or animal models. These include cardiovascular disease, allergic inflammatory disease, transplantation, neuroinflammation, cancer and HIV-associated disease. Discussion focuses on therapeutic directions in which the rapidly evolving chemokine field appears to be headed.

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Ontogeny and behaviour of early macrophages in the zebrafish embryo.

Philippe Herbomel, Christine Thisse, B Thisse (1999)

In the zebrafish embryo, the only known site of hemopoieisis is an intra-embryonic blood island at the junction between trunk and tail that gives rise to erythroid cells. Using video-enhanced differential interference contrast microscopy, as well as in-situ hybridization for the expression of two new hemopoietic marker genes, draculin and leucocyte-specific plastin, we show that macrophages appear in the embryo at least as early as erythroid cells, but originate from ventro-lateral mesoderm situated at the other end of the embryo, just anterior to the cardiac field. These macrophage precursors migrate to the yolksac, and differentiate. From the yolksac, many invade the mesenchyme of the head, while others join the blood circulation. Apart from phagocytosing apoptotic corpses, these macrophages were observed to engulf and destroy large amounts of bacteria injected intravenously; the macrophages also sensed the presence of bacteria injected into body cavities that are isolated from the blood, migrated into these cavities and eradicated the microorganisms. Moreover, we observed that although only a fraction of the macrophage population goes to the site of infection, the entire population acquires an activated behaviour, similar to that of activated macrophages in mammals. Our results support the notion that in vertebrate embryos, macrophages endowed with proliferative capacity arise early from the hemopoietic lineage through a non-classical, rapid differentiation pathway, which bypasses the monocytic series that is well-documented in adult hemopoietic organs.

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Author and article information

Contributors

Qing Cai: cai.qing@sibcb.ac.cn

Yuanyuan Li: esily520@gmail.com

Gang Pei: gpei@sibs.ac.cn

Journal

Journal ID (nlm-ta): J Neuroinflammation

Journal ID (iso-abbrev): J Neuroinflammation

Title: Journal of Neuroinflammation

Publisher: BioMed Central (London )

ISSN (Electronic): 1742-2094

Publication date (Electronic): 24 March 2017

Publication date PMC-release: 24 March 2017

Publication date Collection: 2017

Volume: 14

Electronic Location Identifier: 63

Affiliations

[1 ]ISNI 0000000119573309, GRID grid.9227.e, State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, , Chinese Academy of Sciences, ; 320 Yueyang Road, Shanghai, 200031 China

[2 ]ISNI 0000000119573309, GRID grid.9227.e, , Graduate School, University of Chinese Academy of Sciences, Chinese Academy of Sciences, ; 320 Yueyang Road, Shanghai, 200031 China

[3 ]ISNI 0000000123704535, GRID grid.24516.34, School of Life Science and Technology, and the Collaborative Innovation Center for Brain Science, , Tongji University, ; Shanghai, 200092 China

Article

Publisher ID: 839

DOI: 10.1186/s12974-017-0839-0

PMC ID: 5364682

PubMed ID: 28340576

SO-VID: 2fdeed95-786f-478a-bbcc-1d93fb2ae201

License:

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

History

Date received : 9 October 2016

Date accepted : 13 March 2017

Funding

Funded by: FundRef http://dx.doi.org/10.13039/501100003399, Science and Technology Commission of Shanghai Municipality;

Award ID: 14DZ1900402

Award ID: 15JC1400202

Award Recipient : Gang Pei

Funded by: FundRef http://dx.doi.org/10.13039/501100002855, Ministry of Science and Technology of the People's Republic of China;

Award ID: 2015CB964502

Award Recipient : Gang Pei

Custom metadata

ScienceOpen disciplines: Neurosciences

Keywords: microglia,ganoderma lucidum polysaccharides,neuroinflammation,behavioural response,amyloid beta

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ScienceOpen disciplines: Neurosciences

Keywords: microglia, ganoderma lucidum polysaccharides, neuroinflammation, behavioural response, amyloid beta

Polysaccharides from Ganoderma lucidum attenuate microglia-mediated neuroinflammation and modulate microglial phagocytosis and behavioural response

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Abstract

Background

Methods

Results

Conclusions

Electronic supplementary material

Related collections

Functional role of amyloid

Most cited references 38

Reciprocal regulation between resting microglial dynamics and neuronal activity in vivo.

Chemokines and disease.

Ontogeny and behaviour of early macrophages in the zebrafish embryo.

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