Dataset Information

G-Protein-Coupled Receptor SRBC-48 Protects against Dendrite Degeneration and Reduced Longevity Due to Infection.

ABSTRACT: Increasing evidence suggests that deficient immune modulation and microbial infections underline neurodegeneration, but the mechanisms remain obscure. Here, we show that the G-protein-coupled receptor (GPCR) SRBC-48, which belongs to the class BC serpentine receptors, has a protective role in Caenorhabditis elegans dendrite degeneration caused by Pseudomonas aeruginosa infection. Our results indicate that SRBC-48 functions in a cell-autonomous manner in AWC neurons to protect against infection-associated dendrite degeneration. The absence of SRBC-48 results in a reduced lifespan caused by a pathogen infection early in life that induces dendrite degeneration. The decreased longevity in animals deficient in SRBC-48 is due to uncontrolled activation of immune genes, particularly those regulated by the FOXO family transcription factor DAF-16 that is part of the insulin/insulin-like growth factor (IGF)-1 receptor homolog DAF-2. These results reveal how an infection early in life can not only induce dendrite degeneration but also reduce lifespan.

SUBMITTER: Kaur S

PROVIDER: S-EPMC7304231 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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G-Protein-Coupled Receptor SRBC-48 Protects against Dendrite Degeneration and Reduced Longevity Due to Infection.

Kaur Supender S Aballay Alejandro A

Cell reports 20200501 7

Increasing evidence suggests that deficient immune modulation and microbial infections underline neurodegeneration, but the mechanisms remain obscure. Here, we show that the G-protein-coupled receptor (GPCR) SRBC-48, which belongs to the class BC serpentine receptors, has a protective role in Caenorhabditis elegans dendrite degeneration caused by Pseudomonas aeruginosa infection. Our results indicate that SRBC-48 functions in a cell-autonomous manner in AWC neurons to protect against infection-a ...[more]

PMID: 32433971

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Project description:Oxidative stress and inflammation play key roles in the light damage (LD) model of photoreceptor degeneration, as well as in age-related macular degeneration (AMD). We sought to investigate whether Berberine (BBR), an antioxidant herb extract, would protect the retina against light-induced degeneration. To accomplish this, Balb/c mice were treated with BBR or PBS via gavage for 7 days, and then were placed in constant cool white light-emitting diode (LED) light (10,000 lux) for 4 h. Retinal function and degeneration were evaluated by histology, electroretinography (ERG) and optical coherence tomography (OCT) at 7d after LD. Additionally, mRNA levels of cell-type specific, antioxidant, and inflammatory genes were compared 7d after LD. Photoreceptor DNA fragmentation was assessed via the terminal deoxynucleotidyl transferase dUTP nick end-labeling (TUNEL) assay. LD resulted in substantial photoreceptor-specific cell death. Histological analysis using plastic sections showed dosing with BBR preserved photoreceptors. The ERG analysis demonstrated functional protection by BBR in rod-b, -a, and cone-b waves. In OCT images, mice receiving PBS showed severe thinning and disorganization of the photoreceptor layer 7 days after LD, whereas mice treated with BBR had significantly less thinning and disorganization. Consistent with OCT results, the mRNA levels of Rho in the NSR, and Rpe65 and Mct3 in the RPE, were significantly higher in mice treated with BBR. The numbers of TUNEL-positive photoreceptors were significantly decreased in BBR-treated mice. The retinal mRNA levels of oxidative stress genes, the number of microglia/macrophages, and the malondialdehyde (MDA) immunolabeling were significantly lower in BBR-treated mice compared to controls 48 h after LD, which indicates oxidative stress was reduced by BBR in light-damaged eyes. In conclusion, systemic BBR is protective against light-induced retinal degeneration associated with diminished oxidative stress in the retina. These results suggest that BBR may be protective against retinal diseases involving oxidative stress.

Dataset Information

G-Protein-Coupled Receptor SRBC-48 Protects against Dendrite Degeneration and Reduced Longevity Due to Infection.

Publications

G-Protein-Coupled Receptor SRBC-48 Protects against Dendrite Degeneration and Reduced Longevity Due to Infection.

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