Toxoplasma gondii is a major cause of congenital brain disease. T. gondii infection in the developing fetus frequently results in major neural developmental damage; however, the effects of the parasite infection on the neural stem cells, the key players in fetal brain development, still remain elusive. This study is aiming to explore the role of T. gondii infection on differentiation of neural stem cells (NSCs) and elucidate the underlying molecular mechanisms that regulate the inhibited differentiation of NSCs induced by the infection. Using a differentiation medium, i.e. , DMEM: F12 (1:1 mixture) supplemented with 2% N2, C17.2 neural stem cells (NSCs) were able to differentiate to neurons and astrocytes, respectively evidenced by immunofluorescence staining of differentiation markers including βIII-tubulin and glial fibrillary acidic protein (GFAP). After 5-day culture in the differentiation medium, the excreted-secreted antigens of T. gondii (Tg-ESAs) significantly down-regulated the protein levels of βIII-tubulin and GFAP in C17.2 NSCs in a dose-dependent manner. The protein level of β-catenin in the nucleus of C17.2 cells treated with both wnt3a (a key activator for Wnt/β-catenin signaling pathway) and Tg-ESAs was significantly lower than that in the cells treated with only wnt3a, but significantly higher than that in the cells treated with only Tg-ESAs. In conclusion, the ESAs of T. gondii RH blocked the differentiation of C17.2 NCSs and downregulated the expression of β-catenin, an essential component of Wnt/β-catenin signaling pathway. The findings suggest a new mechanism underlying the neuropathogenesis induced by T. gondii infection, i.e. inhibition of the differentiation of NSCs via blockade of Wnt/β-catenin signaling pathway, such as downregulation of β-catenin expression by the parasite ESAs.
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http://dx.doi.org/10.1016/j.bbrc.2016.03.076 | DOI Listing |
Nat Commun
December 2024
Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.
Currently there are no effective treatments for an array of neurodegenerative disorders to a large part because cell-based models fail to recapitulate disease. Here we develop a reproducible human iPSC-based model where laser axotomy causes retrograde axon degeneration leading to neuronal cell death. Time-lapse confocal imaging revealed that damage triggers an apoptotic wave of mitochondrial fission proceeding from the site of injury to the soma.
View Article and Find Full Text PDFFront Bioeng Biotechnol
December 2024
Department of Orthopedics, The First Affiliated Hospital of Soochow University, Soochow University, Suzhou, Jiangsu, China.
In mammalian species, neural tissues cannot regenerate following severe spinal cord injury (SCI), for which stem cell transplantation is a promising treatment. Neural stem cells (NSCs) have the potential to repair SCI; however, in unfavourable microenvironments, transplanted NSCs mainly differentiate into astrocytes rather than neurons. In contrast, bone mesenchymal stem cells (BMSCs) promote the differentiation of NSCs into neurons and regulate inflammatory responses.
View Article and Find Full Text PDFStem Cell Res Ther
December 2024
Departments of Neurosurgery, The First Center of Chinese, PLA General Hospital, Beijing, China.
Background: Treatment of peripheral nerve defects is a major concern in regenerative medicine. This study therefore aimed to explore the efficacy of a neural graft constructed using adipose mesenchymal stem cells (ADSC), acellular microtissues (MTs), and chitosan in the treatment of peripheral nerve defects.
Methods: Stem cell therapy with acellular MTs provided a suitable microenvironment for axonal regeneration, and compensated for the lack of repair cells in the neural ducts of male 8-week-old Sprague Dawley rats.
J Nutr
December 2024
Faculty of Pharmacy, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Japan. Electronic address:
Background: Food-derived nucleic acids exhibit various biological activities and may act as nutrients. Oral ingestion of the nucleic acid fraction (NAF) of salmon milt extract hydrolysates enhances cognitive function in mice although their active ingredients have not yet been identified, and detailed mechanisms of action are unknown.
Objective: To identify active ingredients enhancing cognitive function contained in the NAF and its possible underlying mechanism.
Front Biosci (Schol Ed)
December 2024
Laboratory of Intracellular Membranes Dynamics, Institute of Cytology of the Russian Academy of Sciences, 194064 Saint Petersburg, Russia.
Background: Real-time reverse transcription quantitative polymerase chain reaction (RT-qPCR) is a powerful tool for analysing target gene expression in biological samples. To achieve reliable results by RT-qPCR, the most stable reference genes must be selected for proper data normalisation, particularly when comparing cells of different types. We aimed to choose the least variable candidate reference genes among eight housekeeping genes tested within a set of human cancer cell lines (HeLa, MCF-7, SK-UT-1B, A549, A431, SK-BR-3), as well as four lines of normal, non-malignant mesenchymal stromal cells (MSCs) of different origins.
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