Cadmium is a highly toxic heavy metal that is capable of accumulating in the body via direct exposure or through the alimentary and respiratory tract, leading to neurodegeneration. In this article, we show that the application of CdCl (0.001-0.005mM) for 48h induced high dose-dependent death rate of cultured cerebellar granule neurons (CGNs). Unlike Trolox or vitamin E, antioxidant N-acetyl-l-cysteine (NAC, 1mM) and Mn (0.0025-0.005mM) significantly protected CGNs from this toxic effect. Using Fluo-4 AM, measurements of intracellular calcium ions demonstrated that 24h-exposure to Cd induced intensive increase of Fluo-4 fluorescence in neurons accompanied by mitochondria swelling. These data imply that the cadmium-induced Ca increase is an important element in the death of neurons due to toxic effect of cadmium and the mechanism of protective action of manganese and NAC is mediated by the prevention of increase in calcium levels.
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http://dx.doi.org/10.1016/j.tox.2017.10.017 | DOI Listing |
Proc Natl Acad Sci U S A
January 2025
Department of Human Molecular Genetics and Biochemistry, Faculty of Health & Medical Sciences, Tel Aviv University, Tel Aviv 69978, Israel.
Ataxia-telangiectasia (A-T) is a pleiotropic genome instability syndrome resulting from the loss of the homeostatic protein kinase ATM. The complex phenotype of A-T includes progressive cerebellar degeneration, immunodeficiency, gonadal atrophy, interstitial lung disease, cancer predisposition, endocrine abnormalities, chromosomal instability, radiosensitivity, and segmental premature aging. Cultured skin fibroblasts from A-T patients exhibit premature senescence, highlighting the association between genome instability, cellular senescence, and aging.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
Department of Clinical Biochemistry and Pharmacology, Faculty of Health Sciences, Zlotowski Center for Neuroscience and Zelman Center-The School of Brain Sciences and Cognition, Ben-Gurion University of the Negev, Beer-Sheva 8410501, Israel.
This narrative review examines lithium's effects on immune function, inflammation and cell survival, particularly in bipolar disorder (BD) in in vitro studies, animal models and clinical studies. In vitro studies show that high lithium concentrations (5 mM, beyond the therapeutic window) reduce interleukin (IL)-1β production in monocytes and enhance T-lymphocyte resistance, suggesting a protective role against cell death. Lithium modulates oxidative stress in lipopolysaccharide (LPS)-activated macrophages by inhibiting nuclear factor (NF)-ƙB activity and reducing nitric oxide production.
View Article and Find Full Text PDFSci Rep
January 2025
Children's Research Center, Division of Oncology, University Children's Hospital Zürich, Zürich, Switzerland.
De-regulated protein expression contributes to tumor growth and progression in medulloblastoma (MB), the most common malignant brain tumor in children. MB is associated with impaired differentiation of specific neural progenitors, suggesting that the deregulation of proteins involved in neural physiology could contribute to the transformed phenotype in MB. Calsynthenin 1 (CLSTN1) is a neuronal protein involved in cell-cell interaction, vesicle trafficking, and synaptic signaling.
View Article and Find Full Text PDFJ Craniofac Surg
January 2025
Department of Neurosurgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Objective: To confirm the incidence of subcutaneous effusion secondary to cerebrospinal fluid leakage after craniotomy, analyze the risk factors for cerebrospinal fluid leakage leading to subcutaneous effusion, summarize the underlying causes of its occurrence and explore the corresponding treatment strategies.
Methods: A retrospective analysis was conducted on 757 patients who underwent craniotomy at our hospital from January to December 2023. The authors documented the sex, age, surgical characteristics, and history of chronic diseases for all patients, including those who developed subcutaneous effusion secondary to cerebrospinal fluid leakage.
Commun Biol
December 2024
Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
Brain-derived neurotrophic factor (BDNF) plays important roles in brain development and neural function. Constitutive knockout of the splicing regulator RBM4 reduces BDNF expression in the developing brain and causes cerebellar hypoplasia, an autism-like feature. Here, we show that Rbm4 knockout induced intron 6 retention of Hsf1, leading to downregulation of HSF1 protein and its downstream target BDNF.
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