S100 calcium-binding protein A8 (S100A8), a danger-associated molecular pattern, has emerged as an important mediator of the pro-inflammatory response. Some S100 proteins play a prominent role in neuroinflammatory disorders and increase the secretion of pro-inflammatory cytokines in microglial cells. The aim of this study was to determine whether S100A8 induced neuronal apoptosis during cerebral hypoxia and elucidate its mechanism of action. In this study, we reported that the S100A8 protein expression was increased in mouse neuronal and microglial cells when exposed to hypoxia, and induced neuroinflammation and neuronal apoptosis. S100A8, secreted from neurons under hypoxia, activated the secretion of tumor necrosis factor (TNF-α) and interleukin-6 (IL-6) through phosphorylation of extracellular-signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) in microglia. Also, phosphorylation of ERK via the TLR4 receptor induced the priming of the NLRP3 inflammasome. The changes in Cyclooxygenase-2 (COX-2) expression, a well-known inflammatory activator, were regulated by the S100A8 expression in microglial cells. Knockdown of S100A8 levels by using shRNA revealed that microglial S100A8 expression activated COX-2 expression, leading to neuronal apoptosis under hypoxia. These results suggested that S100A8 may be an important molecule for bidirectional microglia-neuron communication and a new therapeutic target for neurological disorders caused by microglial inflammation during hypoxia.
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http://dx.doi.org/10.3390/ijms22031205 | DOI Listing |
Cell Rep
January 2025
Department of Human Biology, Faculty of Natural Sciences, University of Haifa, Haifa 34988, Israel. Electronic address:
The elimination of superfluous neurons via apoptosis and subsequent glial phagocytosis is crucial for the development of the central nervous system (CNS). In Drosophila, two glial phagocytic receptors, six-microns-under (SIMU) and Draper, mediate the phagocytosis of apoptotic neurons during embryogenesis. However, in simu;draper double-mutant embryos, some apoptotic neurons are still engulfed by the glia, suggesting the involvement of additional receptors.
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Department of Medical Biochemistry, Faculty of Medicine, Kahramanmaraş Sütçü İmam University, Kahramanmaraş, Turkey.
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January 2025
Laboratory of Exercise and Neurobiology, School of Physical Education and Sports Science, South China Normal University, Guangzhou, 510006, Guangdong, China.
Repeated closed-head injuries (rCHI) from activities like contact sports, falls, military combat, and traffic accidents pose a serious risk due to their cumulative impact on the brain. Often, rCHI is not diagnosed until symptoms of irreversible brain damage appear, highlighting the need for preventive measures. This study assessed the prophylactic efficacy of remote photobiomodulation (PBM) targeted at the lungs against rCHI-induced brain injury and associated behavioral deficits.
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January 2025
Department of Medical Elementology and Toxicology, Jamia Hamdard, Delhi, India, 110062. Electronic address:
Malathion is an organophosphate compound widely used as an insecticide in the agriculture sector and is toxic to humans and other mammals. Although several studies have been conducted at different level in different animal models. But there is no work has been conducted on the toxicological correlation from cellular to behavioral level on surviving species model.
View Article and Find Full Text PDFExp Neurol
January 2025
Department of Rehabilitation Medicine, The First Hospital of China Medical University, Shenyang, China. Electronic address:
Spinal cord injury (SCI) is a neurodegenerative disease, with a high disability rate. According to the results of mRNA-seq, transcription factor AP-2 Beta (TFAP2B) is a potential target of repetitive Transspinal Magnetic Stimulation (rTSMS) in SCI treatment. Our results demonstrated that rTSMS significantly improved motor function and promoted neuronal survival post-SCI.
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