D-Galactose-Induced Accelerated Aging Model on Auditory Cortical Neurons by Regulating Oxidative Stress and Apoptosis in Vitro

Sertoli cell -only syndrome (SCOS) is a type of testicular pathological failure that causes male infertility and no effective treatment strategy, is available for this condition. Moreover, the molecular mechanism underlying its development remains unknown. We identified DExD/H-Box helicase 58 (DDX58) as a key gene in SCOS based on four datasets of testicular tissue samples obtained from the Gene Expression Synthesis database. DDX58 was significantly upregulated in SCOS testicular Sertoli cells. Moreover, high expression of DDX58 was positively correlated with the expression of several testicular inflammatory factors, such as IL -1β, IL-18, and IL-6. Interestingly, DDX58 could be induced in the D-galactose (D-gal)-stimulated TM4 cell injury model. Whereas silencing of DDX58 inhibited D-gal -mediated p65 expression, inflammatory cytokine release, and growth arrest. Mechanistically, we found that DDX58 acts as an RNA-binding protein, which enhances p65 expression by promoting mRNA stability. Furthermore, p65 gene silencing decreased the expression of inflammatory cytokines and inhibition of cell growth in D-gal-induced cells. In conclusion, our findings demonstrate that DDX58 promotes inflammatory responses and growth arrest in SCOS Sertoli cells by stabilizing p65 mRNA. Accordingly, the DDX58/p65 regulatory axis might be a therapeutic target for SCOS.

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“…Studies have reported that D-gal can induce cellular oxidative stress, mitochondrial damage, inflammation, and tissue damage ( 45 – 47 ).…”

Section: Resultsmentioning

confidence: 99%

DDX58 expression promotes inflammation and growth arrest in Sertoli cells by stabilizing p65 mRNA in patients with Sertoli cell-only syndrome

et al. 2023

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“…To demonstrate the batch-parallel processing capacity of our strategy in organoid modeling, we constructed several types of disease models, including models of aging, neuroinflammation, and oxidative stress, and investigated their cellular and molecular characteristics using our strategy. We modeled oxidative stress using 1 mM hydrogen peroxide [ 22 ], neuroinflammation using 20 μg/mL lipopolysaccharides [ 23 ], aging using 60 mg/mL D-galactose [ 24 ], and aging therapy using 50 ng/mL neural growth factor (NGF) as a treatment [ 25 ]. To overcome the diffusion limitations, we selected the basal drug concentration from the 2D culture modeling and increased it by 2~3 times compared to the 2D culture modeling.…”

Section: Resultsmentioning

confidence: 99%

Cerebral Organoid Arrays for Batch Phenotypic Analysis in Sections and Three Dimensions

Chen,

Ma,

Deng

et al. 2023

IJMS

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Organoids can recapitulate human-specific phenotypes and functions in vivo and have great potential for research in development, disease modeling, and drug screening. Due to the inherent variability among organoids, experiments often require a large sample size. Embedding, staining, and imaging each organoid individually require a lot of reagents and time. Hence, there is an urgent need for fast and efficient methods for analyzing the phenotypic changes in organoids in batches. Here, we provide a comprehensive strategy for array embedding, staining, and imaging of cerebral organoids in both agarose sections and in 3D to analyze the spatial distribution of biomarkers in organoids in situ. We constructed several disease models, particularly an aging model, as examples to demonstrate our strategy for the investigation of the phenotypic analysis of organoids. We fabricated an array mold to produce agarose support with microwells, which hold organoids in place for live/dead imaging. We performed staining and imaging of sectioned organoids embedded in agarose and 3D imaging to examine phenotypic changes in organoids using fluorescence micro-optical sectioning tomography (fMOST) and whole-mount immunostaining. Parallel studies of organoids in arrays using the same staining and imaging parameters enabled easy and reliable comparison among different groups. We were able to track all the data points obtained from every organoid in an embedded array. This strategy could help us study the phenotypic changes in organoids in disease models and drug screening.

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“…Through nonenzymatic glycation, the physiological nutrition D‐galactose (D‐gal) interacts with free amines of amino acids in proteins to produce advanced glycation end products (Bhaumik et al, 2019; Conte et al, 2021). Additionally, it is a well‐known activator of oxidative senescence and has been extensively employed to establish animal ageing models and cellular ageing models in vitro (de Almeida Rezende et al, 2021; Ullah et al, 2020; Zhao et al, 2022). In this study, D‐gal‐treated mice were utilized to create ageing models that included symptoms of ageing including learning and memory loss, slowing of movement, and hair thinning.…”

Section: Discussionmentioning

confidence: 99%

“…At 37 C for 2 h. Nuclei were stained with 4 0 ,6-diamidino-2-phenylindole (DAPI) for the last 5 min. Images were captured by a fluorescence microscope (Olympus, Japan) (Zhao et al, 2022).…”

Section: Immunofluorescence Stainingmentioning

confidence: 99%

Ginsenoside Rg1 attenuates D‐galactose‐induced neural stem cell senescence via the Sirt1‐Nrf2‐BDNF pathway

Hu,

Ran,

Wang

et al. 2023

Eur J of Neuroscience

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With the ageing of society's population, neurodegenerative diseases have become an important factor affecting the quality of life and mortality in the elderly. Since its physiopathological processes are complex and the authorized medications have recently been shown to have several adverse effects, the development of safe and efficient medications is urgently needed. In this study, we looked at how ginsenoside Rg1 works to postpone neural stem cell ageing and brain ageing, giving it a solid scientific foundation for use as a therapeutic therapy for neurodegenerative diseases.

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D-Galactose-Induced Accelerated Aging Model on Auditory Cortical Neurons by Regulating Oxidative Stress and Apoptosis in Vitro

Cited by 9 publications

References 70 publications

DDX58 expression promotes inflammation and growth arrest in Sertoli cells by stabilizing p65 mRNA in patients with Sertoli cell-only syndrome

DDX58 expression promotes inflammation and growth arrest in Sertoli cells by stabilizing p65 mRNA in patients with Sertoli cell-only syndrome

Cerebral Organoid Arrays for Batch Phenotypic Analysis in Sections and Three Dimensions

Ginsenoside Rg1 attenuates D‐galactose‐induced neural stem cell senescence via the Sirt1‐Nrf2‐BDNF pathway

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