Neuroscience
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The nociceptive withdrawal reflex (NWR) is a behavioral response to protect the body from noxious stimuli. The spatial characteristics of the stimulus modulate the reflex response to prevent damage to the affected tissue. Interneurons in the deep dorsal horn in the spinal cord encode the relationship between stimulus characteristics and the magnitude of the NWR and are also likely integrating spatial information of the nociceptive stimulus. ⋯ In contrast, the NWR recorded during the attention task did not differ from baseline. These results further support that the spinal NWR pathway is under descending control which can be modulated by cognitive processes. The NWRs recorded over both proximal and distal muscles were similarly affected by the tasks, suggesting that the descending control affects the lower leg spinal system, with no discrimination between spinal segments.
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Cerebral ischemia/reperfusion is the major pathophysiological process in stroke and could lead to severe and permanent disability. The current study aimed to investigate the effects of dedicator of cytokinesis 2 (DOCK2) on cerebral ischemia/reperfusion-induced cerebral injury. We established a mouse middle cerebral artery occlusion (MCAO) model with suture-occluded method in vivo. ⋯ Subsequently, we found that the loss of DOCK2 upregulated the expression of p-STAT6. DOCK2 knockdown-induced microglial cell polarization towards M2 phenotype was partly abrogated by the STAT6 inhibitor AS1517499. In conclusion, DOCK2 downregulation protected against cerebral ischemia/reperfusion by modulating microglia polarization via the activation of the STAT6 signaling pathway.
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In early psychosis there are alterations in the static functional interaction between the salience network (SN) and higher-order cognitive networks. It is unclear whether these changes extend to the dynamic functional connectivity (dFC) of the SN, and whether the dFC between the SN and low-order networks (e.g., sensory networks) is affected. This study examined the temporal properties of the functional connectivity of the SN in individuals with early psychosis. ⋯ We found compared with the HC, in the FES and CHR groups the bilateral AI and ACC showed less variability in dFC with regions in the visual network; the variability between the ACC and visual regions in the FES group was less than that of the CHR; and in the FES and CHR groups the variability in dFC was higher between the right AI and the left precuneus (a core region of the default mode network). This study confirmed abnormality of dynamic functional interaction between the SN and the DMN in psychosis. More importantly, the disruption of communication between the SN and the lower-order brain network is another important aspect of the neural basis of psychosis.
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Under normal conditions, dopamine (DA) clearance after release largely depends on uptake by the DA transporter (DAT). DAT expression/activity is reduced in some neuropsychiatric and neurological disorders. Our aim was to characterize the behavioral, neurochemical and electrophysiological effects of eliminating DAT in a novel knockout rat model we generated using CRISPR/Cas9. ⋯ However, D2 receptor-mediated inhibition of firing (by quinpirole or L-DOPA) was blunted in DAT-KO rats, while GABAB-mediated inhibition was preserved. We have also provided new data for the DAT-KO rat regarding the effects of slowing DA diffusion with dextran and blocking organic cation transporter 3 with corticosterone. Together, our results validate our DAT-KO rat and provide new insights into the mechanisms of chronic dysregulation of the DA system by addressing several unresolved issues in previous studies with other DAT-KO models.
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Vanillin has been reported to reduce hippocampal neuronal death in rat models of global cerebral ischemia. However, the immunoregulatory mechanism of vanillin in ischemic stroke is still unclear. To investigate the role of vanillin in a mouse model of ischemic stroke, we administered vanillin to mice after transient middle cerebral artery occlusion (tMCAO) by tail vein injection. ⋯ Similar effects were observed using the in vitro LPS-stimulated microglia cell model. Moreover, the reduced expression of proinflammatory cytokines in the vanillin group was related to TLR4/NF-κB signaling. Taken together, the findings suggest that vanillin decreased microglial activation by inhibiting the TLR4 /NF-κB signaling pathway, which reduced expression of proinflammatory cytokines IL-1β and TNF-α, and finally reduced the infarct volume and improved motor function in tMCAO mice.