Antibiotics Treatment Modulates Microglia–Synapses Interaction

Cordella, Federica; Sanchini, Caterina; Rosito, Maria; Ferrucci, Laura; Pediconi, Natalia; Cortese, Barbara; Guerrieri, Francesca; Pascucci, Giuseppe Rubens; Antonangeli, Fabrizio; Peruzzi, Giovanna; Giubettini, Maria; Basilico, Bernadette; Pagani, Francesca; Grimaldi, Alfonso; D’Alessandro, Giuseppina; Limatola, Cristina; Ragozzino, Davide; Angelantonio, Silvia Di

doi:10.3390/cells10102648

Cited by 27 publications

(13 citation statements)

References 60 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In a recent study by Cordella et al, male mice fed a standard diet and administered gentamicin and vancomycin in drinking water supplemented with sugar revealed increased microglial density, but no change to morphology, in the hippocampus [ 61 ]. This study only focused on male mice and therefore, sex differences under the experimental parameters were not assessed.…”

Section: Discussionmentioning

confidence: 99%

Sex differences in the fecal microbiome and hippocampal glial morphology following diet and antibiotic treatment

et al. 2022

View full text Add to dashboard Cite

Rising obesity rates have become a major public health concern within the United States. Understanding the systemic and neural effects of obesity is crucial in designing preventive and therapeutic measures. In previous studies, administration of a high fat diet has induced significant weight gain for mouse models of obesity. Interestingly, sex differences in high-fat diet-induced weight gain have been observed, with female mice gaining significantly less weight compared to male mice on the same high-fat diet. It has also been observed that consumption of a high-fat diet can increase neurogliosis, but the mechanism by which this occurs is still not fully understood. Recent research has suggested that the gut microbiome may mediate diet-induced glial activation. The current study aimed to (1) analyze changes to the gut microbiome following consumption of a high fat (HF) diet as well as antibiotic treatment, (2) evaluate hippocampal microgliosis and astrogliosis, and (3) identify sex differences within these responses. We administered a low fat (Research Diets D12450 K) or high fat diet (Research Diets D12451) to male and female C57Bl/6 mice for sixteen weeks. Mice received an antibiotic cocktail containing 0.5g/L of vancomycin, 1.0 g/L ampicillin, 1.0 g/L neomycin, and 1.0 g/L metronidazole in their drinking water during the last six weeks of the study and were compared to control mice receiving normal drinking water throughout the study. We observed a significant reduction in gut microbiome diversity for groups that received the antibiotic cocktail, as determined by Illumina next-generation sequencing. Male mice fed the HF diet (± antibiotics) had significantly greater body weights compared to all other groups. And, female mice fed the low fat (LF) diet and administered antibiotics revealed significantly decreased microgliosis and astrogliosis in the hippocampus compared to LF-fed females without antibiotics. Interestingly, male mice fed the LF diet and administered antibiotics revealed significantly increased microgliosis, but decreased astrogliosis, compared to LF-fed males without antibiotics. The observed sex differences in LF-fed mice given antibiotics brings forward questions about sex differences in nutrient metabolism, gut microbiome composition, and response to antibiotics.

show abstract

Section: Discussionmentioning

confidence: 99%

Sex differences in the fecal microbiome and hippocampal glial morphology following diet and antibiotic treatment

et al. 2022

View full text Add to dashboard Cite

show abstract

“…To identify the microglial cytoskeleton in retina we used cx3cr1 gfp/+ mice, which constitutively express GFP in microglia. As expected, retinal microglia from control cx3cr1 gfp/+ mice displayed a highly ramified morphology (Figure S3E), typical of homeostatic surveillant cells (Grimaldi et al ., 2018; Basilico et al ., 2019; Cordella et al ., 2021). More importantly, confocal immunofluorescence analysis of GM130 signal in retinal GFP positive microglia confirmed the presence of isolated Golgi outposts also in the processes of homeostatic microglia residing in tissue (5 ± 1 per cell, n = 11; Figure 3G, S3F and S3G).…”

Section: Resultsmentioning

confidence: 99%

Microglia reactivity entails microtubule remodeling from acentrosomal to centrosomal arrays

Rosito¹,

Sanchini²,

Gosti³

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

Microglia reactivity triggered by proinflammatory signaling entails a large-scale remodeling of cellular geometry, but the role of the microtubule cytoskeleton during these changes remains unexplored. Here we show that reactive proinflammatory microglia provide a heretofore unique example of microtubule reorganization from a non-centrosomal array of parallel and stable microtubules to a radial array of more dynamic microtubules. While in the homeostatic state microglia nucleate microtubules at Golgi outposts, proinflammatory signaling induces recruitment of nucleating material nearby the centrosome and inhibition of de novo formed pericentrosomal microtubule-organizing centers enhances NLRP3 inflammasome activation and secretion of the interleukin IL-1β. Our results demonstrate that remodeling of the microtubule cytoskeleton is a hallmark of proinflammatory microglia reactivity and suggest that pericentrosomal microtubule nucleating material maturation may offer a valuable target to modulate cytokine-mediated inflammatory responses in chronic disease and tissue injury.

show abstract

“…In adult healthy mice, two-weeks of ABX treatment influence hippocampal microglial density, reducing their basal patrolling activity, and impairing process rearrangement in response to damages ( 130 ). In addition, ABX treatment induced a reduction of spontaneous postsynaptic glutamatergic currents and in general, of synaptic connectivity ( 110 ).…”

Section: Gut Microbiota Modulation By Antibiotics In Healthy and Dise...mentioning

confidence: 99%

Microglial cells: Sensors for neuronal activity and microbiota-derived molecules

D’Alessandro

Marrocco²,

Limatola³

2022

Front. Immunol.

Self Cite

View full text Add to dashboard Cite

Microglial cells play pleiotropic homeostatic activities in the brain, during development and in adulthood. Microglia regulate synaptic activity and maturation, and continuously patrol brain parenchyma monitoring for and reacting to eventual alterations or damages. In the last two decades microglia were given a central role as an indicator to monitor the inflammatory state of brain parenchyma. However, the recent introduction of single cell scRNA analyses in several studies on the functional role of microglia, revealed a not-negligible spatio-temporal heterogeneity of microglial cell populations in the brain, both during healthy and in pathological conditions. Furthermore, the recent advances in the knowledge of the mechanisms involved in the modulation of cerebral activity induced by gut microbe-derived molecules open new perspectives for deciphering the role of microglial cells as possible mediators of these interactions. The aim of this review is to summarize the most recent studies correlating gut-derived molecules and vagal stimulation, as well as dysbiotic events, to alteration of brain functioning, and the contribution of microglial cells.

show abstract

Antibiotics Treatment Modulates Microglia–Synapses Interaction

Cited by 27 publications

References 60 publications

Sex differences in the fecal microbiome and hippocampal glial morphology following diet and antibiotic treatment

Sex differences in the fecal microbiome and hippocampal glial morphology following diet and antibiotic treatment

Microglia reactivity entails microtubule remodeling from acentrosomal to centrosomal arrays

Microglial cells: Sensors for neuronal activity and microbiota-derived molecules

Contact Info

Product

Resources

About