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Aluminum (Al) is considered one of the environmental risk factors for Alzheimer's disease (AD). The present study aims to establish a zebrafish AD model induced by Al and explore if necrostation-1 (Nec-1), a specific inhibitor of necroptosis, is effective in relieving learning and memory deficits in the zebrafish AD models. We treated adult zebrafish with aluminum trichloride at various doses for 1 month, followed by a T-maze test to evaluate learning and memory performance. Al concentration, levels of acetylcholine (Ach), and AD-related protein and gene expression in the brain tissue were evaluated in the zebrafish AD models. Our results demonstrated that in the brain tissue of Al-treated zebrafish, Al accumulated, Ach levels decreased, and AD-related genes and proteins increased. As a result, the learning and memory performance of Al-treated zebrafish was impaired. This suggested that a zebrafish AD model was established. To test the effect of Nec-1 on the zebrafish AD model, we added Nec-1 into the culture medium of the Al-treated adult zebrafish. The results demonstrated that Nec-1 could relive the learning and memory deficits, enhance Ach levels and the numbers of neural cells, and impact necroptosis-related gene expression. We concluded that Nec-1 could reverse Al-induced learning and memory impairment and had potential theoretical value in the zebrafish AD model.
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http://dx.doi.org/10.1007/s12640-021-00463-6 | DOI Listing |
EMBO J
September 2025
Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan.
During a critical period of postnatal brain development, neural circuits undergo significant refinement coincident with widespread alternative splicing of hundreds of genes, which undergo altered splice site selection for the generation of isoforms essential for synaptic plasticity. Here, we reveal that neuronal activity-dependent phosphorylation of paxillin at its serine 119 (p-paxillin) acts as a molecular switch in the nucleus for the control of alternative splicing during this period. We show that following NMDA receptor activation, nuclear p-paxillin is recruited to nuclear speckles, where it interacts with splicing factors, such as U2AFs.
View Article and Find Full Text PDFExp Neurobiol
August 2025
Department of Biological Sciences, Konkuk University, Seoul 05029, Korea.
This study investigated the learning strategy preferences of 11-month-old APP/PS1 double transgenic (Tg) mice, a well-established murine model of Alzheimer's disease (AD). APP/PS1 Tg and non-Tg control mice were serially trained in visual and hidden platform tasks in the Morris water maze. APP/PS1 Tg mice performed poorly in visual platform training compared with non-Tg mice but performed as well as non-Tg mice in hidden platform training.
View Article and Find Full Text PDFJ Agric Food Chem
September 2025
Department of Food Science and Engineering, Ningbo University, Ningbo 315211, P.R. China.
Sleep deprivation (SD) is a major contributor to cognitive impairment, often accompanied by central neuroinflammation and gut microbiota dysbiosis. The tryptophan (TRP) pathway, activated via indoleamine 2,3-dioxygenase (IDO), serves as a critical link between immune activation and neuronal damage. Umbelliferone (UMB), a naturally occurring coumarin compound, possesses anti-inflammatory, antioxidant, and microbiota-modulating properties.
View Article and Find Full Text PDFPLoS One
September 2025
College of Business Administration, Northern Border University (NBU), Arar, Kingdom of Saudi Arabia.
The increasing dependence on cloud computing as a cornerstone of modern technological infrastructures has introduced significant challenges in resource management. Traditional load-balancing techniques often prove inadequate in addressing cloud environments' dynamic and complex nature, resulting in suboptimal resource utilization and heightened operational costs. This paper presents a novel smart load-balancing strategy incorporating advanced techniques to mitigate these limitations.
View Article and Find Full Text PDFJ Neurophysiol
September 2025
School of Psychological and Cognitive Sciences, Peking University, Beijing, China.
Limiting cognitive resources negatively impacts motor learning, but its cognitive mechanism is still unclear. Previous studies failed to differentiate its effect on explicit (or cognitive) and implicit (or procedural) aspects of motor learning. Here, we designed a dual-task paradigm requiring participants to simultaneously perform a visual working memory task and a visuomotor rotation adaptation task to investigate how cognitive load differentially impacted explicit and implicit motor learning.
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