Neuroscience
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Cerebral ischemia-reperfusion injury (CI/RI) injury is a common feature of ischemic stroke which occurs when the blood supply is restored after a period of ischemia in the brain. Reduced blood-flow to the brain during CI/RI compromises neuronal cell health as a result of mitochondrial dysfunction, oxidative stress, cytokine production, inflammation and tissue damage. ⋯ A range of drug and interventional therapies have emerged that can alleviate CI/RI mediated oxidative stress, inflammation and apoptosis in the brain. Herein, we review recent studies on CI/RI interventions for which a mechanism of action has been described and the potential of these therapeutic modalities for future use in the clinic.
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Developmental sevoflurane exposure leads to widespread neuronal cell death known as sevoflurane-induced neurotoxicity (SIN). Receptor-interacting protein kinase-3 (RIPK3) and mixed lineage kinase domain-like (MLKL)-driven necroptosis plays an important role in cell fate. Previous research has shown that inhibition of RIPK1 activity alone did not attenuate SIN. ⋯ Finally, the administration of the RIPK3 inhibitor GSK'872 relieved sevoflurane-induced spatial and emotional disorders without influence on locomotor activity. Altogether, these results illustrate that ZBP1 senses cytosolic mtDNA to induce RIPK3/MLKL-driven necroptosis in SIN. Elucidating the role of necroptosis in SIN will provide new insights into understanding the mechanism of anesthetic exposure in the developing brain.
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Embodied cognition research indicates that sensorimotor training can influence action concept processing. Yet, most studies employ isolated (pseudo)randomized stimuli and require repetitive single-effector responses, thus lacking ecological validity. Moreover, the neural signatures of these effects remain poorly understood. ⋯ Conversely, static videogame playing yielded no specific effect on any linguistic category and did not modulate functional connectivity. Together, these findings suggest that action-verb processing and key neural correlates can be focally influenced by full-body motor training in a highly ecological setting. Our study illuminates the role of situated experience and sensorimotor circuits in action-concept processing, addressing calls for naturalistic insights on language embodiment.
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Morphine and other opioid analgesics are the drugs of election to treat moderate-to-severe pain, and they elicit their actions by binding to the opioid receptors. Cocaine is a potent inhibitor of dopamine, serotonin, and noradrenaline reuptake, as it blocks DAT, the dopamine transporter, causing an increase in the local concentration of these neurotransmitters in the synaptic cleft. The molecular effects of these drugs have been studied in specific brain areas or nuclei, but the systemic effects in the whole organism have not been comprehensively analyzed. ⋯ An RNAseq assay was performed with tissues extracts from zebrafish embryos treated from 5 hpf (hours post fertilization) to 72 hpf, and the most representative deregulated genes were experimentally validated by qPCR. We have found changes in the expression of genes related to lipid metabolism, chemokine receptor ligands, visual system, hemoglobins, and metabolic detoxification pathways. Besides, morphine and cocaine modified the global DNA methylation pattern in zebrafish embryos, which would explain the changes in gene expression elicited by these two drugs of abuse.
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Inflammation and resolution are highly programmed processes involving a plethora of immune cells. Lipid mediators synthesized from arachidonic acid metabolism play a pivotal role in orchestrating the signaling cascades in the game of inflammation. The majority of the studies carried out so far on inflammation were aimed at inhibiting the generation of inflammatory molecules, whereas recent research has shifted more towards understanding the resolution of inflammation. ⋯ Resolvins derived from these fatty acids comprise the D-and E-series resolvins. A growing body of evidence using in vitro and in vivo models has revealed the pro-resolving and anti-inflammatory potential of resolvins. This systematic review sheds light on the synthesis, specialized receptors, and resolution of inflammation mediated by resolvins in Alzheimer's and Parkinson's disease.