Neuroscience
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The nucleotide oligomerization domain (NOD)-like receptor (NLR) pyrin domain-containing protein 1 (NLRP1) inflammasome has been shown to contribute to brain injury after ischemic stroke. Our previous study showed that microRNA-9a-5p (miR-9a-5p) ameliorates ischemic injury by regulating neuronal autophagy in rats subjected to middle cerebral artery occlusion (MCAO) surgery. The aims of this study were to investigate whether miR-9a-5p can influence the NLRP1 inflammasome following ischemic stroke and to clarify the mechanism involved. ⋯ Further investigation showed that NLRP1 was a target of miR-9a-5p and was downregulated by miR-9a-5p overexpression and upregulated by miR-9a-5p inhibition. Moreover, overexpression of miR-9a-5p not only decreased the levels of NLRP1, ASC and precursor caspase-1 but also reduced the levels of IL-1β and IL-18 in MCAO rats and OGD cells. Therefore, we conclude that miR-9a-5p is involved in NLRP1 inflammasome-mediated ischemic injury, which further suggests that the overexpression of miR-9 may be an effective way to ameliorate brain injury following ischemic stroke.
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The role of stress in altering fear memory is not well understood. Since individual variations in stress reactivity exist, and stress alters fear memory, exposing individuals with differing stress-reactivity to repeated stress would affect their fear memory to various degrees. We explored this question using the average stress-reactive Fisher 344 (F344) rat strain and the Wistar-Kyoto (WKY) strain with its heightened stress-reactivity. ⋯ In contrast, DEGs unique to the F344 and the WKY stress responses are divergent in their functionality and networks, beyond that of strain differences in their non-stressed state. These results suggest that in some individuals chronic or repeated stress, different from the original fear memory-provoking stress, can attenuate prior fear memory. Furthermore, the novel blood DEGs can report on the general state of stress of the individual, or can be associated with individual variation in stress-responsiveness.
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The tryptophan metabolite kynurenic acid (KYNA) may play an important role in normal and abnormal cognitive processes, most likely by interfering with α7 nicotinic and NMDA receptor function. KYNA is formed from its immediate precursor kynurenine either by non-enzymatic oxidation or through irreversible transamination by kynurenine aminotransferases. In the mammalian brain, kynurenine aminotransferase II (KAT II) is the principal enzyme responsible for the neosynthesis of rapidly mobilizable KYNA, and therefore constitutes an attractive target for pro-cognitive interventions. ⋯ Furthermore, GSH failed to S-glutathionylate recombinant human KAT II treated with the dithiocarbamate drug disulfiram. Shown by microdialysis in the prefrontal cortex of rats treated with kynurenine (50 mg/kg, i.p.), peripheral administration of NAC (500 mg/kg, i.p., 120 and 60 min before the application of kynurenine) reduced KYNA neosynthesis by ∼50%. Together, these results suggest that NAC exerts its neurobiological effects at least in part by reducing cerebral KYNA formation via KAT II inhibition.
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Randomized Controlled Trial
Effects of Nicotine on Task Switching and Distraction in Non-smokers. An fMRI Study.
Nicotine improves sustained attention and reduces distractor interference, promoting cognitive stability. While stable performance may be beneficial in some situations, others require flexible updating of task demands. Frontoparietal networks, basal ganglia and thalamus contribute to an optimal balance of stable and flexible performance. ⋯ However, a brain-behaviour correlation analysis revealed that the nicotine-induced alterations of distractor costs correlated positively with distractor-related neural activity in the right intraparietal sulcus and the right pulvinar nucleus of the thalamus. We suggest that a nicotinic contribution to balancing stability and flexibility is weak in young healthy non-smokers. The brain-behaviour correlations imply that if nicotine reduces distractor interference, the modulation is found in thalamic-parietal networks.
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Randomized Controlled Trial
Domain-specific involvement of the posterior parietal cortex in attention network and attentional control of ADHD: A randomized, cross-over, sham-controlled tDCS study.
Transcranial direct current stimulation (tDCS) has been increasingly used in attention-deficit hyperactivity disorder (ADHD) with mixed results. Previous tDCS studies merely targeted the dorsolateral prefrontal cortex and right inferior frontal gyrus with partial or no improving effects on cognitive deficits respectively. Posterior parietal cortex is another region involved in attentional functioning of ADHD, however, its contribution to ADHD attention functions has not been explored in tDCS studies. ⋯ No significant effect on shifting attention and response inhibition was found. Our findings indicate a domain-specific involvement of the r-PPC in attention orienting network of ADHD children. Activation of the r-PPC improves bottom-up but hinders top-down attentional control suggesting a critical role of the r-PPC in ADHD bottom-up attentional control.