scholarly journals Cytokine Signalling at the Microglial Penta-Partite Synapse

2021 ◽  
Vol 22 (24) ◽  
pp. 13186
Author(s):  
Jason Abbas Aramideh ◽  
Andres Vidal-Itriago ◽  
Marco Morsch ◽  
Manuel B. Graeber

Microglial cell processes form part of a subset of synaptic contacts that have been dubbed microglial tetra-partite or quad-partite synapses. Since tetrapartite may also refer to the presence of extracellular matrix components, we propose the more precise term microglial penta-partite synapse for synapses that show a microglial cell process in close physical proximity to neuronal and astrocytic synaptic constituents. Microglial cells are now recognised as key players in central nervous system (CNS) synaptic changes. When synaptic plasticity involving microglial penta-partite synapses occurs, microglia may utilise their cytokine arsenal to facilitate the generation of new synapses, eliminate those that are not needed anymore, or modify the molecular and structural properties of the remaining synaptic contacts. In addition, microglia–synapse contacts may develop de novo under pathological conditions. Microglial penta-partite synapses have received comparatively little attention as unique sites in the CNS where microglial cells, cytokines and other factors they release have a direct influence on the connections between neurons and their function. It concerns our understanding of the penta-partite synapse where the confusion created by the term “neuroinflammation” is most counterproductive. The mere presence of activated microglia or the release of their cytokines may occur independent of inflammation, and penta-partite synapses are not usually active in a neuroimmunological sense. Clarification of these details is the main purpose of this review, specifically highlighting the relationship between microglia, synapses, and the cytokines that can be released by microglial cells in health and disease.

2020 ◽  
Vol 20 (5) ◽  
pp. 654-669
Author(s):  
Thea Magrone ◽  
Manrico Magrone ◽  
Emilio Jirillo

Mast cells (MCs) have recently been re-interpreted in the context of the immune scenario in the sense that their pro-allergic role is no longer exclusive. In fact, MCs even in steady state conditions maintain homeostatic functions, producing mediators and intensively cross-talking with other immune cells. Here, emphasis will be placed on the array of receptors expressed by MCs and the variety of cytokines they produce. Then, the bulk of data discussed will provide readers with a wealth of information on the dual ability of MCs not only to defend but also to offend the host. This double attitude of MCs relies on many variables, such as their subsets, tissues of residency and type of stimuli ranging from microbes to allergens and food antigens. Finally, the relationship between MCs with basophils and eosinophils will be discussed.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Toru Murakawa-Hirachi ◽  
Yoshito Mizoguchi ◽  
Masahiro Ohgidani ◽  
Yoshinori Haraguchi ◽  
Akira Monji

AbstractThe pathophysiology of Alzheimer’s disease (AD) is related to neuroinflammatory responses mediated by microglia. Memantine, an antagonist of N-methyl-d-aspartate (NMDA) receptors used as an anti-Alzheimer’s drug, protects from neuronal death accompanied by suppression of proliferation and activation of microglial cells in animal models of AD. However, it remains to be tested whether memantine can directly affect microglial cell function. In this study, we examined whether pretreatment with memantine affects intracellular NO and Ca2+ mobilization using DAF-2 and Fura-2 imaging, respectively, and tested the effects of memantine on phagocytic activity by human β-Amyloid (1–42) phagocytosis assay in rodent microglial cells. Pretreatment with memantine did not affect production of NO or intracellular Ca2+ elevation induced by TNF in rodent microglial cells. Pretreatment with memantine also did not affect the mRNA expression of pro-inflammatory (TNF, IL-1β, IL-6 and CD45) or anti-inflammatory (IL-10, TGF-β and arginase) phenotypes in rodent microglial cells. In addition, pretreatment with memantine did not affect the amount of human β-Amyloid (1–42) phagocytosed by rodent microglial cells. Moreover, we observed that pretreatment with memantine did not affect 11 major proteins, which mainly function in the phagocytosis and degradation of β-Amyloid (1–42), including TREM2, DAP12 and neprilysin in rodent microglial cells. To the best of our knowledge, this is the first report to suggest that memantine does not directly modulate intracellular NO and Ca2+ mobilization or phagocytic activity in rodent microglial cells. Considering the neuroinflammation hypothesis of AD, the results might be important to understand the effect of memantine in the brain.


Biomolecules ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 868
Author(s):  
Jiayang Zhang ◽  
Ruoyu Sun ◽  
Tingting Jiang ◽  
Guangrui Yang ◽  
Lihong Chen

Blood pressure (BP) follows a circadian rhythm, it increases on waking in the morning and decreases during sleeping at night. Disruption of the circadian BP rhythm has been reported to be associated with worsened cardiovascular and renal outcomes, however the underlying molecular mechanisms are still not clear. In this review, we briefly summarized the current understanding of the circadian BP regulation and provided therapeutic overview of the relationship between circadian BP rhythm and cardiovascular and renal health and disease.


2021 ◽  
Vol 11 (12) ◽  
pp. 5718
Author(s):  
Nicola Gaetano Gatta ◽  
Andrea Parente ◽  
Francesca Guida ◽  
Sabatino Maione ◽  
Vittorio Gentile

Background: Tissue type 2 transglutaminase (TG2, E.C. 2.3.2,13) is reported to be involved in the phagocytosis of apoptotic cells in mouse microglial BV2 cells and peripheral macrophages. In this study, by using lipopolysaccharide (LPS)- or amyloid-β 1-42 (Aβ 1-42) peptide-stimulated microglial cell line BV2 and mouse primary microglial cells, we examined the effects of different neuronutraceutical compounds, such as curcumin (Cu) and N-Palmitoylethanolamine (PEA), known for their anti-inflammatory activity, on TG2 and several inflammatory or neuroprotective biomarker expressions. Methods: Mouse BV2 cells were treated with LPS or Aβ1-42 in the presence of curcumin or PEA, in order to evaluate the expression of TG2 and other inflammatory or neuroprotective markers using Real Time-PCR and Western blot analyses. Results: Curcumin and PEA were capable of reducing TG2 expression in mouse microglial cells during co-treatment with LPS or Aβ 1-42. Conclusions: The results show the role of TG2 as an important marker of neuroinflammation and suggest a possible use of curcumin and PEA in order to reduce LPS- or Aβ1-42-induced TG2 overexpression in mouse microglial cells.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ryo Matsuzaki ◽  
Shigekatsu Suzuki ◽  
Haruyo Yamaguchi ◽  
Masanobu Kawachi ◽  
Yu Kanesaki ◽  
...  

Abstract Background Pyrenoids are protein microcompartments composed mainly of Rubisco that are localized in the chloroplasts of many photosynthetic organisms. Pyrenoids contribute to the CO2-concentrating mechanism. This organelle has been lost many times during algal/plant evolution, including with the origin of land plants. The molecular basis of the evolutionary loss of pyrenoids is a major topic in evolutionary biology. Recently, it was hypothesized that pyrenoid formation is controlled by the hydrophobicity of the two helices on the surface of the Rubisco small subunit (RBCS), but the relationship between hydrophobicity and pyrenoid loss during the evolution of closely related algal/plant lineages has not been examined. Here, we focused on, the Reticulata group of the unicellular green algal genus Chloromonas, within which pyrenoids are present in some species, although they are absent in the closely related species. Results Based on de novo transcriptome analysis and Sanger sequencing of cloned reverse transcription-polymerase chain reaction products, rbcS sequences were determined from 11 strains of two pyrenoid-lacking and three pyrenoid-containing species of the Reticulata group. We found that the hydrophobicity of the RBCS helices was roughly correlated with the presence or absence of pyrenoids within the Reticulata group and that a decrease in the hydrophobicity of the RBCS helices may have primarily caused pyrenoid loss during the evolution of this group. Conclusions Although we suggest that the observed correlation may only exist for the Reticulata group, this is still an interesting study that provides novel insight into a potential mechanism determining initial evolutionary steps of gain and loss of the pyrenoid.


Reproduction ◽  
2021 ◽  
Vol 162 (3) ◽  
pp. 181-191
Author(s):  
Jessica Ispada ◽  
Aldcejam Martins da Fonseca Junior ◽  
Otávio Luiz Ramos Santos ◽  
Camila Bruna de Lima ◽  
Erika Cristina dos Santos ◽  
...  

Metabolic and molecular profiles were reported as different for bovine embryos with distinct kinetics during the first cleavages. In this study, we used this same developmental model (fast vs slow) to determine if the relationship between metabolism and developmental kinetics affects the levels of acetylation or tri-methylation at histone H3 lysine 9 (H3K9ac and H3K9me3, respectively). Fast and slow developing embryos presented different levels of H3K9ac and H3K9me3 from the earliest stages of development (40 and 96 hpi) and up to the blastocyst stage. For H3K9me3, both groups of embryos presented a wave of demethylation and de novo methylation, although it was more pronounced in fast than slow embryos, resulting in blastocysts with higher levels of this mark. The H3K9ac reprogramming profile was distinct between kinetics groups. While slow embryos presented a wave of deacetylation, followed by an increase in this mark at the blastocyst stage, fast embryos reduced this mark throughout all the developmental stages studied. H3K9me3 differences corresponded to writer and eraser transcript levels, while H3K9ac patterns were explained by metabolism-related gene expression. To verify if metabolic differences could alter levels of H3K9ac, embryos were cultured with sodium-iodoacetate (IA) or dichloroacetate (DCA) to disrupt the glycolytic pathway or increase acetyl-CoA production, respectively. IA reduced H3K9ac while DCA increased H3K9ac in blastocysts. Concluding, H3K9me3 and H3K9ac patterns differ between embryos with different kinetics, the second one explained by metabolic pathways involved in acetyl-CoA production. So far, this is the first study demonstrating a relationship between metabolic differences and histone post-translational modifications in bovine embryos.


PARADIGMI ◽  
2011 ◽  
pp. 11-28
Author(s):  
Elselijn Kingma

Philosophy of Medicine is considered a new and emerging discipline. This paper presents an overview of philosophy of medicine, discusses its relation to bioethics and to other areas of philosophy, and introduces three potential topics for research in the philosophy of medicine: concepts of health and disease, the relationship between medicine and psychiatry, and the problems of medical knowledge and evidence.


2015 ◽  
Vol 12 (1) ◽  
pp. 177-191 ◽  
Author(s):  
C. Wu ◽  
I. Pullinen ◽  
S. Andres ◽  
G. Carriero ◽  
S. Fares ◽  
...  

Abstract. Impacts of soil moisture on de novo monoterpene (MT) emissions from Holm oak, European beech, Scots pine, and Norway spruce were studied in laboratory experiments. The volumetric water content of the soil, Θ, was used as the reference quantity to parameterize the dependency of MT emissions on soil moisture and to characterize the severity of the drought. When Θ dropped from 0.4 m3 × m−3 to ~0.2 m3 × m−3 slight increases of de novo MT emissions were observed but with further progressing drought the emissions decreased to almost zero. In most cases the increases of MT emissions observed under conditions of mild drought were explainable by increases of leaf temperature due to lowered transpirational cooling. When Θ fell below certain thresholds, MT emissions decreased simultaneously with Θ and the relationship between Θ and MT emissions was approximately linear. The thresholds of Θ (0.044–0.19 m3 × m−3) were determined, as well as other parameters required to describe the soil moisture dependence of de novo MT emissions for application in the Model of Emissions of Gases and Aerosols from Nature, MEGAN. A factorial approach was found appropriate to describe the impacts of Θ, temperature, and light. Temperature and Θ influenced the emissions largely independently from each other, and, in a similar manner, light intensity and Θ acted independently on de novo MT emissions. The use of Θ as the reference quantity in a factorial approach was tenable in predicting constitutive de novo MT emissions when Θ changed on a time scale of days. Empirical parameterization with Θ as a reference was only unsuccessful when soil moisture changed rapidly


Molecules ◽  
2019 ◽  
Vol 24 (3) ◽  
pp. 448 ◽  
Author(s):  
Pengjun Lu ◽  
Ruqian Wang ◽  
Changqing Zhu ◽  
Xiumin Fu ◽  
Shasha Wang ◽  
...  

Plastids are sites for carotenoid biosynthesis and accumulation, but detailed information on fruit plastid development and its relation to carotenoid accumulation remains largely unclear. Here, using Baisha (BS; white-fleshed) and Luoyangqing (LYQ; red-fleshed) loquat (Eriobotrya japonica), a detailed microscopic analysis of plastid development during fruit ripening was carried out. In peel cells, chloroplasts turned into smaller chromoplasts in both cultivars, and the quantity of plastids in LYQ increased by one-half during fruit ripening. The average number of chromoplasts per peel cell in fully ripe fruit was similar between the two cultivars, but LYQ peel cell plastids were 20% larger and had a higher colour density, associated with the presence of larger plastoglobules. In flesh cells, chromoplasts could be observed only in LYQ during the middle and late stages of ripening, and the quantity on a per-cell basis was higher than that in peel cells, but the size of chromoplasts was smaller. It was concluded that chromoplasts are derived from the direct conversion of chloroplasts to chromoplasts in the peel, and from de novo differentiation of proplastids into chromoplasts in flesh. The relationship between plastid development and carotenoid accumulation is discussed.


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