Glucocorticoid‐mediated modulation of morphological changes associated with aging in microglia

Olst, Lynn van; Bielefeld, Pascal; Fitzsimons, Carlos P.; Vries, Helga E. de; Schouten, Marijn

doi:10.1111/acel.12790

Cited by 33 publications

(29 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The factors controlling microglial morphology and functions are manifold and may include well-known modulators of the immune system like glucocorticoids. In mouse hippocampus, for example, an experimental increase of glucocorticoid level in young mice (where glucocorticoid levels are normally low) enhanced microglial ramification (Van Olst et al, 2018). Amoeboid microglia are characterized by migratory movements forming pseudopods.…”

Section: Morphological and Functional Signs Of Microglial Activationmentioning

confidence: 99%

Microglia in neuropathology caused by protozoan parasites

et al. 2019

View full text Add to dashboard Cite

Involvement of the central nervous system (CNS) is the most severe consequence of some parasitic infections. Protozoal infections comprise a group of diseases that together affect billions of people worldwide and, according to the World Health Organization, are responsible for more than 500000 deaths annually. They include African and American trypanosomiasis, leishmaniasis, malaria, toxoplasmosis, and amoebiasis. Mechanisms underlying invasion of the brain parenchyma by protozoa are not well understood and may depend on parasite nature: a vascular invasion route is most common. Immunosuppression favors parasite invasion into the CNS and therefore the host immune response plays a pivotal role in the development of a neuropathology in these infectious diseases. In the brain, microglia are the resident immune cells active in defense against pathogens that target the CNS. Beside their direct role in innate immunity, they also play a principal role in coordinating the trafficking and recruitment of other immune cells from the periphery to the CNS. Despite their evident involvement in the neuropathology of protozoan infections, little attention has given to microglia–parasite interactions. This review describes the most prominent features of microglial cells and protozoan parasites and summarizes the most recent information regarding the reaction of microglial cells to parasitic infections. We highlight the involvement of the periphery–brain axis and emphasize possible scenarios for microglia–parasite interactions.

show abstract

Section: Morphological and Functional Signs Of Microglial Activationmentioning

confidence: 99%

Microglia in neuropathology caused by protozoan parasites

et al. 2019

View full text Add to dashboard Cite

show abstract

“…These neuroendocrine receptors can modulate microglial functions such as their release of inflammatory mediators (i.e. IL-1β, IL-6, TNF-α) during a LPS immune challenge [87][88][89], their morphology [90], cellular dynamics and proliferation [89]. Moreover, neuroendocrine receptors are differently expressed by microglia between the sexes [91].…”

Section: Discussionmentioning

confidence: 99%

Microglial and peripheral immune priming is partially sexually dimorphic in adolescent mouse offspring exposed to maternal high-fat diet

Bordeleau

Lacabanne

Cossío

et al. 2020

Preprint

View full text Add to dashboard Cite

Background Maternal nutrition is critical for proper fetal development. While increased nutrient intake is essential during pregnancy, an excessive consumption of certain nutrients, like fat, can lead to long-lasting detrimental consequences on the offspring. Animal work investigating the consequences of maternal high-fat diet (mHFD) revealed in the offspring a maternal immune activation (MIA) phenotype associated with increased inflammatory signals. This inflammation was proposed as one of the mechanisms causing neuronal circuit dysfunction, notably in the hippocampus, by altering the brain-resident macrophages –microglia. However, the understanding of mechanisms linking inflammation and microglial activities to pathological brain development remains limited. We hypothesized that mHFD-induced inflammation could prime microglia by altering their specific gene expression signature, population density and/or functions. Methods We used an integrative approach combining molecular techniques, confocal and scanning electron microscopy, to investigate the effects of mHFD vs control diet on inflammatory priming, as well as microglial density, distribution, morphology, and ultrastructure in mice. These analyses were performed on the mothers, and/or their adolescent offspring at postnatal day (P) 30. Results Our study revealed that mHFD results in MIA defined by increased circulating levels of interleukin (IL)-6 in the mothers. This phenotype was associated with an exacerbated inflammatory response to peripheral lipopolysaccharide in mHFD-exposed offspring of both sexes. Microglial morphology was also altered and there were increased microglial interactions with astrocytes in the hippocampus CA1 of mHFD-exposed male offspring, as well as decreased microglia-associated extracellular space pockets in the same region of mHFD-exposed offspring of the two sexes. A decreased mRNA expression of the inflammatory-regulating cytokine Tgfb1 and microglial receptors Tmem119, Trem2 and Cx3cr1 was additionally measured in the hippocampus of mHFD-exposed offspring, especially in males. Conclusions Here, we described how dietary habits during pregnancy and nurturing, particularly the consumption of an enriched fat diet, can influence peripheral immune priming in the offspring. We also found that microglia are affected in terms of gene expression signature, morphology and interactions with the hippocampal parenchyma, in a partially sexually dimorphic manner, which may contribute to the adverse neurodevelopmental outcomes on the offspring.

show abstract

“…Senescence can be induced by various intrinsic and extrinsic triggers. Extensive use of dexamethasone has been associated with cellular senescence and aging-related pathological process in vivo and in vitro [25,26]. However, the potential relationship between cellular senescence and development retardation in bone induced by PDE remains unclear.…”

Section: Introductionmentioning

confidence: 99%

Cellular senescence mediates the detrimental effect of prenatal dexamethasone exposure on postnatal long bone growth in mice offspring

Chai

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Prenatal dexamethasone exposure (PDE) induces low birth weight and retardation of fetal bone development which are associated with lower peak bone mass in adult offspring. Here we evaluated whether and how PDE affects postnatal long bone growth in mice offspring. Methods: Pregnant mice were injected subcutaneously with dexamethasone (1.2 mg/kg/day) every morning from gestational day (GD) 12-14. Femurs and tibias of 2-, 4-, 6-, and 12-week-old female offspring were harvested for histological, immunofluorescence, flow cytometric analysis, or microcomputed tomography (μCT) measurement. Results: PDE leads to impaired bone remodeling as well as decreased bone mass in the long bone of female mice offspring. During postnatal bone growth, significant decrease of CD45-CD29+CD105+Sca-1+ bone marrow mesenchymal stem cells (BMSCs) and CD45-Nestin+ cells, loss of type H vessels as well as increment of cellular senescence were found in metaphysis of long bone in mice offspring after PDE. We further show that eliminating the excessive senescent cells with dasatinib (5 mg/kg/day) and quercetin (50 mg/kg/day) during GD 12-14 rescues the above toxic effect of PDE on the postnatal long bone growth in female mice offspring. Conclusion: Cellular senescence mediates the toxic effect of PDE on postnatal long bone growth in mice offspring, and inhibition of cellular senescence may be proposed for treating the retardation of bone growth caused by PDE.

show abstract

Glucocorticoid‐mediated modulation of morphological changes associated with aging in microglia

Cited by 33 publications

References 17 publications

Microglia in neuropathology caused by protozoan parasites

Microglia in neuropathology caused by protozoan parasites

Microglial and peripheral immune priming is partially sexually dimorphic in adolescent mouse offspring exposed to maternal high-fat diet

Cellular senescence mediates the detrimental effect of prenatal dexamethasone exposure on postnatal long bone growth in mice offspring

Contact Info

Product

Resources

About