Neuroscience
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Astrocytes and microglia appear central to the initiation and progression of neuroinflammation in Alzheimer's disease (AD). In this study, inflammation was mimicked by Aβ1-42 treatment of rat astrocytes (RA) and N9 microglia cell lines. Inflammation induced by Aβ1-42 can be inhibited by pyrrolidine dithiocarbamic acid (PDTC), indicating that the NF-κB signal pathway is involved in inflammation. ⋯ In addition, Res decreased the nuclear translocation of NF-κB/p65 when checked by immunofluorescence. Furthermore, Res increased the expression of NF-κB/p65 and decreased the expression of p-IκB in the cytoplasm in both RA and N9 microglia. Taken together, the present data indicate that Res reduces inflammation in RA and N9 microglia, and the anti-NF-κB signal pathway may be one of the target mechanisms.
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Human amyloid β1-42 (hAβ1-42) peptides are known to self-aggregate into oligomers that contribute to the degeneration of neurons and development of Alzheimer's disease (AD) pathology. Unlike humans, rodents do not develop AD, possibly due to differences in three amino acids (R5G, Y10F and H13R) within the hydrophilic N-terminal domain of Aβ1-42. This is partly supported by evidence that hAβ1-42 is more prone to fibrillization and has a higher cellular toxicity than rodent Aβ1-42 (rAβ1-42). ⋯ Interestingly, the mutants are still able to aggregate into oligomers, which are predominantly larger than those comprised of hAβ1-42. Our cell viability experiments further showed a rank order of oligomer toxicity of hAβ1-42 > rAβ1-42 ≫ mutant Aβ1-42, suggesting that toxicity can be influenced by N-terminal Aβ1-42 mutations via reduction of fibril formation and/or alteration of oligomer size. These results, taken together, confirm that N-terminal mutations can affect Aβ fibril and oligomer formation with reduced toxicity despite lying outside the core amyloid region of Aβ peptide.
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Oxidative stress exhibits a central role in the course of amyotrophic lateral sclerosis (ALS), a progressive neurodegenerative disease commonly found to include a copper/zinc superoxide dismutase (SOD1) gene mutation. Fisetin, a natural antioxidant, has shown benefits in varied neurodegenerative diseases. The possible effect of fisetin in ALS has not been clarified as of yet. ⋯ Furthermore, fisetin increased the expression of phosphorylated ERK and upregulated antioxidant factors, which were reversed by MEK/ERK inhibition. Finally, fisetin reduced the levels of both mutant and wild-type hSOD1 in vivo and in vitro, as well as the levels of detergent-insoluble hSOD1 proteins. The results indicate that fisetin protects cells from ROS damage and improves the pathological behaviors caused by oxidative stress in disease models related to SOD1 gene mutations probably by activating ERK, thereby providing a potential treatment for ALS.
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In the primary visual cortex (V1), neuronal responses to stimuli within the receptive field (RF) are modulated by stimuli in the RF surround. A common effect of surround modulation is surround suppression, which is dependent on the feature difference between stimuli within and surround the RF and is suggested to be involved in the perceptual phenomenon of figure-ground segregation. In this study, we examined the relationship between feature-specific surround suppression of V1 neurons and figure detection behavior based on figure-ground feature difference. ⋯ Consistent with the behavioral performance, the sensitivity of V1 neurons to RF-surround phase difference could be influenced by stimulus contrast. Furthermore, inhibiting V1 by optogenetically activating either parvalbumin (PV)- or somatostatin (SOM)-expressing inhibitory neurons both decreased the behavioral performance of figure detection. Thus, the phase-specific surround suppression in V1 represents a neural correlate of figure detection behavior based on figure-ground phase discontinuity.
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Gait dysfunction, a hallmark of Parkinson's disease, contributes to a relatively high incidence of falling. Gait function is further diminished during the performance of a motor-cognitive task (i.e., dual-task). It is unclear if Parkinson's disease-related dual-task deficits are related to a specific area of cognitive function or are the result of a more global decline in executive function. ⋯ The attention and problem solving task resulted in the greatest number of gait parameter decrements. Results indicated that performance on cognitive tasks remained unchanged from single-task to dual-task conditions. Diminished gait performance under dual-task conditions across different cognitive function domains suggests a global Parkinson's disease-related deficit in information processing and regulation of gait.