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The effect of antibiotics and propionate treatment on astrocyte transcription in APPPS1-21 mice

ABSTRACT: The effect of antibiotics and propionate treatment on astrocyte transcription in APPPS1-21 mice

PROVIDER: PRJNA1254711 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR33289200.fastq.gz	Fastqsanger.gz
	SRR33289201.fastq.gz	Fastqsanger.gz
	SRR33289202.fastq.gz	Fastqsanger.gz
	SRR33289188.fastq.gz	Fastqsanger.gz
	SRR33289189.fastq.gz	Fastqsanger.gz

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The effect of antibiotics and propionate treatment on astrocyte transcription in APPPS1-21 mice

Project description:Previously, we have shown that broad spectrum antibiotic treatment reduces reactive astrocyte phenotypes in the APPPS1-21 model of AD-related amyloidosis. We have also found that antibiotics selectively increases propionate levels and exogenous propionate treatment recapitulates phenotypes observed in antibiotic treated mice. In the current study, we wanted to assess astrocyte transcriptional state using bulk RNA sequencing. To accomplish this we used translating ribosome affinity purification (TRAP) sequencing, a ribosomal protein L10a is fused to eGFP under the control of a cell type specific promoter in a transgenic mouse model. We crossed APPPS1-21 mice to the Aldh1l1-eGFP/Rpl10a bacTRAP mouse model and progeny were treated with antibiotics, propionate, or VHL and performed bulk TRAPseq.

2025-05-01 | GSE295458 | GEO

Single nucleus RNA sequencing of the cortex of antibiotic and vehicle treated APPPS1-21 mice

Project description:Previously, we and others have shown that broad spectrum antibiotic treatment from postnatal day 14-21 reduces neuroinflammation in the APPPS1-21 model of AD-related amyloidosis. In the current study, we used single-nucleus RNA sequencing (snRNAseq) to assess cell-type specific transcriptional changes in antibiotic treated mice and controls. We also assessed changes in astrocyte subclusters in these groups.

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RNAseq of cortex of 6-month old APPPS1 and APPPS1;Apoe-/- mice

Project description:One of the hallmarks of Alzheimer’s disease is the presence of extracellular diffuse and fibrillar plaques predominantly consisting of the amyloid-β (Aβ) peptide. ApoE influences the deposition of amyloid pathology through affecting the clearance and aggregation of monomeric Aβ in the brain. In addition to influencing Aβ metabolism, increasing evidence suggests that apoE influences microglial function in neurodegenerative diseases. Here, we characterize the impact that apoE has on amyloid pathology and the innate immune response in APPPS1∆E9 and APPPS1-21 transgenic mice. We report that Apoe deficiency reduced fibrillar plaque deposition consistent with previous studies. However, fibrillar plaques in Apoe-deficient mice exhibited a striking reduction in plaque compaction. Hyperspectral fluorescent imaging using luminescent conjugated oligothiophenes identified distinct Aβ morphotypes in Apoe-deficient mice. We also observed a significant reduction in fibrillar plaque-associated microgliosis and activated microglial gene expression in Apoe-deficient mice, along with significant increases in dystrophic neurites around fibrillar plaques. Our results suggest that apoE is critical in stimulating the innate immune response to amyloid pathology.

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Transcription profiling of human fetal cerebellum, heart, cerebrum, and cerebrum derived astrocyte cell line from trisomy 21 and trisomy 13 samples

2008-06-11 | E-GEOD-1397 | biostudies-arrayexpress

RNAseq of cortex of 6-month old APPPS1 and APPPS1 Apoe-/- mice

Project description:RNAseq of cortex of 6-month old APPPS1 and APPPS1 Apoe-/- mice

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Single nucleus RNA sequencing of the cortex of antibiotic and vehicle treated APPPS1-21 mice

Project description:Single nucleus RNA sequencing of the cortex of antibiotic and vehicle treated APPPS1-21 mice

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The antimicrobial peptide Esc(1-21)-1c increases susceptibility of Pseudomonas aeruginosa to conventional antibiotics by decreasing the expression of the MexAB-OprM efflux pump

Project description:The increase in bacterial strains resistant to conventional antibiotics is an alarming problem for human health and could lead to pandemics in the future. Among bacterial pathogens responsible for a large variety of severe infections there is Pseudomonas aeruginosa. Therefore, there is an urgent need for new molecules with antimicrobial activity or that can act as adjuvants of antibiotics already in use. In this scenario, antimicrobial peptides (AMPs) hold great promise. Recently, we characterized a frogskin AMP derived from esculentin-1a, namely Esc(1-21)-1c, endowed with antipseudomonal activity without being cytotoxic to human cells. Here, we investigated the effect of combining this peptide with a panel of antibiotics from different classes and found that Esc(1-21)-1c can synergistically inhibit the growth of P. aeruginosa cells with three different antibiotics, including tetracycline. We therefore investigated the underlying mechanism implemented by the peptide using a differential proteomic approach. The data revealed a significant decrease in the production of three proteins belonging to the MexAB-OprM efflux pump upon treatment with sub-inhibitory concentration of Esc(1-21)-1c. Downregulation of these proteins was confirmed by transcriptional analysis and direct measurement of their relative levels in bacterial cells by tandem mass spectrometry analysis in multiple reaction monitoring scan mode. This would increase the intracellular drug content making bacteria more susceptible to the antibiotic. Overall, these results highlight the importance of characterizing new molecules able to synergize with conventional antibiotics, paving the way for the development of alternative therapeutic strategies based on AMP/antibiotic formulations to counteract the emergence of resistant bacterial strains and increase the use of "old" antibiotics in medical practice.

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Project description:Propionate is an abundant carboxylic acid in nature. Microorganisms metabolize propionate aerobically via the 2-methylcitrate pathway. This pathway depends on a series of three reactions in the citric acid cycle that leads to the conversion of succinate to oxaloacetate. Interestingly, the gamma-proteobacterium Escherichia coli can use propionate as a carbon and electron source under oxic but not under anoxic conditions. The typical downregulation of the citric acid cycle under anoxic conditions is only partially responsible for the inability to use propionate under anoxic conditions since an arcA mutant shows very limited growth on propionate. RT-PCR and transcriptomic analysis revealed a post-transcriptional regulation of the prp-genecluster encoding the necessary enzymes for propionate metabolism. The polycistronic mRNA was hydrolyzed in the 3`-5` direction under anoxic conditions. This regulatory strategy is highly constructive because the last gene of the operon encodes the first enzyme of the propionate metabolism. Further analysis revealed that RNase R catalyzes the hydrolysis of the prp transcripts. Consequently, an rnr-deletion strain could metabolize propionate under anoxic conditions. To the best of our knowledge, this is the first study describing the influence of RNase R on the anaerobic metabolism of E. coli.

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bulk RNA sequencing for GL261 cells treated with propionate

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