Neuroscience
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Amyloid β (Aβ) is a pathogenic peptide associated with many neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. The retinal inflammation in response to Aβ is implicated in the pathogenesis of several ocular diseases including age-related macular degeneration, Alzheimer's-related optic neuropathy and glaucoma. In the present study, we found that a single intravitreal injection of oligomeric Aβ1-40 in mouse activated the NLRP3 inflammasome and the NF-κB signaling, induced the production of inflammatory cytokines including TNF-α and IL-6. ⋯ TO90 preserved ERG a- and b-wave amplitudes and reduced the number of Iba1-positive cells in the Aβ1-40-treated retina. Furthermore, TO90 down-regulated the mRNA levels of TNF-α and IL-6, as well as the expressions of p-IκBα, NLRP3, caspase-1 and IL-1β in the Aβ1-40-injected animals. We suggest that activation of LXRα and its target gene ABCA1 exerts potent anti-inflammatory effect on the Aβ-treated retina.
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Prenatal hypoxia induced by transient intrauterine ischemia is a serious clinical problem, and at present, effective treatments are lacking. Currently, it is unknown how prenatal hypoxia affects behaviors in adulthood. Therefore, we developed a mouse model that mimics prenatal hypoxia in humans using uterine artery occlusion in late gestation. ⋯ Neurochemical analysis revealed that dopamine was increased in the female hippocampus, but not in males. Thus, neonatal SSRI treatment decreases dopamine levels in the hippocampus in females selectively. Our findings suggest that prenatal hypoxia is a risk factor for behavioral abnormalities in adulthood, and that neonatal SSRI treatment might have clinical potential for alleviating these long-term behavioral deficits.
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The assessment of mental workload can inform attentional resource allocation during task performance that is essential for understanding the underlying principles of human cognitive-motor behavior. While many studies have focused on mental workload in relation to human performance, a modest body of work has examined it in a motor practice/learning context without considering individual variability. Thus, this work aimed to examine mental workload by employing the NASA TLX as well as the changes in motor performance resulting from the practice of a novel reaching task. ⋯ A secondary cluster analysis was also conducted to identify specific individual patterns of cognitive-motor responses. Overall, both group- and cluster-level analyses revealed that: (i) all participants improved their performance throughout motor practice, and (ii) an increase in mental workload was associated with a reduction of the quality of motor performance along with a slower rate of motor improvement. The results are discussed in the context of the optimal challenge point framework and in particular it is proposed that under the experimental conditions employed here, functional task difficulty: (i) would possibly depend on an individuals' information processing capabilities, and (ii) could be indexed by the level of mental workload which, when excessively heightened can decrease the quality of performance and more generally result in delayed motor improvements.
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In hippocampus, two guanylyl cyclases (NO-GC1 and NO-GC2) are involved in the transduction of the effects of nitric oxide (NO) on synaptic transmission. However, the respective roles of the NO-GC isoforms on synaptic transmission are less clear in other regions of the brain. In the present study, we used knock-out mice deficient for the NO-GC1 isoform (NO-GC1 KO) to analyze its role in the glutamatergic and GABAergic neurotransmission at pyramidal neurons in layers II/III of somatosensory cortex. ⋯ By blocking postsynaptic NMDA receptors, the NMDA receptor-dependent NO signal was shown to be linked to the effect of NO-GC1 on presynaptic GABA release. Of note, the balance between glutamatergic and GABAergic inputs at individual synapses remained unaltered in the NO-GC1 KO mice. In sum, our results indicate a role for cGMP generated by presynaptic localized NO-GC1 to adjust inhibitory and excitatory inputs at individual synapses in the somatosensory cortex.
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Impaired olfaction is associated with a volume decrease in the olfactory bulb as well as in the gray matter of cortical olfactory areas. On the other hand, restitution of an impaired olfaction results in a regain of volume in these regions. Studies investigating similar changes in the cerebral white matter are virtually not existent. ⋯ In the group with relevant olfactory improvement higher values of fractional anisotropy and apparent diffusion coefficient were found in the right parahippocampal area and in the white matter below the left inferior temporal sulcus. Tract-specific diffusion property analysis revealed significant group differences in the cingulate cortex in spatial relationship to the perisplenial cortex. Overall, this prospective study indicates structural changes in white matter after postoperative restoration of olfaction.