Neuroscience
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Emerging evidence suggests that hypoxia-inducible factors (specifically, HIF-1α) and Notch signaling are involved in epileptogenesis and that cross-coupling exists between HIF-1α and Notch signaling in other diseases, including tumors and ischemia. However, the exact molecular mechanisms by which HIF-1α and Notch signaling affect the development of epilepsy, especially regarding neurogenesis, remain unclear. ⋯ The immunoprecipitation data illustrated that HIF-1α activated Notch signaling by physically interacting with the Notch intracellular domain (NICD) in epilepsy. In conclusion, our results suggested that HIF-1α-Notch signaling enhanced neurogenesis in acute epilepsy and that neurogenesis during epileptogenesis was reduced once this pathway was blocked; thus, members of this pathway might be potential therapeutic targets for epilepsy.
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Primary cultures of rat dorsal root ganglia (DRG) consist of neurons, satellite glial cells and a moderate number of macrophages. Measurements of increased intracellular calcium [Ca2+]i induced by stimuli, have revealed that about 70% of DRG neurons are capsaicin-responsive nociceptors, while 10% responded to cooling and or menthol (putative cold sensors). Cultivation of DRG in the presence of a moderate dose of lipopolysaccharide (LPS, 1 µg/ml) enhanced capsaicin-induced Ca2+ signals. ⋯ In the presence of the cytotoxic agent cisplatin (5 or 10 µg/ml), the number of macrophages was decreased significantly, the growth of satellite glial cells was markedly suppressed, but the vitality and stimulus-induced Ca2+ signals of DRG neurons were not impaired. Under these conditions the LPS-induced production and expression of TNF-α and IL-6 were blunted. Our data suggest a potential role for macrophages and satellite glial cells in the initiation of inflammatory processes that develop in sensory ganglia upon injury or exposure to pathogens.
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Detecting morphological changes of dendritic spines in time-lapse microscopy images and correlating them with functional properties such as memory and learning, are fundamental and challenging problems in neurobiology research. In this paper, we propose an algorithm for dendritic spine detection in time series. The proposed approach initially performs spine detection at each time point and improves the accuracy by exploiting the information obtained from tracking of individual spines over time. ⋯ Finally, we determine the spine location more precisely by performing a watershed-geodesic active contour model. We quantitatively assess the performance of the proposed spine detection algorithm based on annotations performed by biologists and compare its performance with the results obtained by the noncommercial software NeuronIQ. Experiments show that our approach can accurately detect and quantify spines in 2-photon microscopy time-lapse data and is able to accurately identify spine elimination and formation.
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Alzheimer's disease (AD) is a progressive neurodegenerative disorder, with no effective method for its treatment so far. The pathogenesis of AD has been reported, but the endogenous metabolic profile and disease-related biomarkers are still not clear. To better understand AD, an AD model induced by injecting β-amyloid 25-35 (Aβ 25-35) solution into bilateral hippocampus was developed on Sprague-Dawley rats. ⋯ The results showed that compared with healthy control rats, AD rats suffered from cognitive dysfunction, hippocampus damage, Aβ formation and tau phosphorylation at 8 weeks after surgery, suggesting that the Aβ25-35-induced AD model was successfully established. In addition, the levels of γ-aminobutyric acid, acetylcholine, glycine, norepinephrine, serotonin, taurine and dopamine decreased and glutamate and aspartic acid increased in hippocampal tissue of AD rats. 45 altered metabolites mainly involved in 8 metabolic pathways were identified as the endogenous biomarkers of AD. According to the analysis of the biological significance of metabolic profiles, the pathogenesis of AD was mainly due to gut microbiome dysbiosis, inhibition of energy metabolism, oxidative stress injury and loss of neuronal protective substances.
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Apolipoprotein E4 (apoE4), one of the three apoE isoforms, is the strongest factor for raising the risk for late-onset Alzheimer's disease (AD) and has been proposed to play a major role in AD pathogenesis. Amyloid-peptide β 42 (Aβ42) has also been proposed to affect neuronal degeneration and AD pathogenesis, possibly by interacting with apoE. Previous studies have shown that the functions of apoE forms can be dictated by their structural and biophysical properties. ⋯ Structural and thermodynamic analyses showed that all three apoE4 mutants have significantly increased α-helical and decreased β-sheet content, have reduced portion of hydrophobic surfaces exposed to the solvent and have a reduced conformational stability during chemical denaturation. Overall, our data highlight a pathogenic role of apoE4 that could be linked to the capacity of the protein to form oligomeric species especially in the presence of Aβ42 and to induce cytotoxicity. Carboxyl-terminal residues L279, K282 or Q284 appear to be involved in the conformation of apoE4 that may underlie the protein's functional properties related to neurotoxicity.