Neuroscience
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Ischemic stroke is a neurological disorder that causes pathological changes by increasing oxidative stress. Retinoic acid is one of the metabolites of vitamin A. It regulates oxidative stress and exerts neuroprotective effects. ⋯ However, the mitigation effects of retinoic acid were lower in thioredoxin siRNA-transfected neurons than in non-transfected neurons. These results demonstrate that retinoic acid regulates oxidative stress and thioredoxin expression, maintains the interaction between thioredoxin and ASK1, and modulates apoptosis-associated proteins. Taken together, these results suggest that retinoic acid has neuroprotective effects by regulating thioredoxin expression and modulating apoptotic pathway.
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Delayed neuronal damage can be caused or aggravated after cerebral ischemia-reperfusion (I/R) injury. Recent studies have shown that glymphatic system dysfunction after cerebral ischemia-reperfusion injury is involved in ischemic brain edema and neuroinflammation, thereby regulating cerebral ischemia-reperfusion injury. The aim of this study is to investigate the changes of glymphatic system after cerebral ischemia-reperfusion injury and whether limb remote ischemic postconditioning (LRIP) can improve the function of glymphatic system to protect the brain. ⋯ Glymphatic system impaired after cerebral ischemia-reperfusion injury in mice. LRIP may play a neuroprotective role by improving glymphatic function after I/R.
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Mitochondrial damage is a central mechanism involved in neurological disorders as Alzheimer's, and Parkinson's diseases and amyotrophic lateral sclerosis. Energy production is the most studied mitochondrial function; however, mitochondria are also involved in processes like calcium buffering homeostasis, and cell death control during apoptosis and necrosis. Using transmission electron microscopy, in this in vivo study in male rats, we describe ultrastructural mitochondrial alterations of spinal motor neurons along chronic AMPA-induced excitotoxicity, which has been described as one of the most relevant mechanisms in ALS disease. ⋯ In addition, by combining the TUNEL assay and immunohistochemistry for mitochondrial enzymes, we show evidence of mitochondrial DNA damage. Evidence of mitochondrial alterations during an AMPA-excitotoxic event is relevant because resembles the mitochondrial alterations previously reported in ALS patients and in transgenic familial ALS models, suggesting that a chronic excitotoxic model can be related to sporadic ALS (as has been shown in recent papers), which represent more than the 90% of the ALS cases. Understanding the mechanisms involved in motor neuron degenerative process, such as the ultrastructural mitochondrial changes permits to design strategies for MN-degeneration treatments in ALS.
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Social buffering is a phenomenon where stress responses are ameliorated by an affiliative conspecific. Our previous findings suggest that the posterior complex of the anterior olfactory nucleus (AOP) is well positioned to participate in the neural mechanisms underlying social buffering. However, the lack of anatomical information prevents us from further estimating the role of the AOP. ⋯ The proportion of double-labeled cells among the tracer-labeled cells was 2.1% ± 1.2%. Taken together, these results suggest that the AOP is predominantly composed of glutamatergic neurons. In addition, the AOP sends mutually independent glutamatergic-predominant projections to the BLA and MeP.
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N6-methyl adenosine (m6A) modification is known to play a crucial role in various aging-related diseases. However, its involvement in presbycusis, a type of age-related hearing loss, is not yet clear. We examined the changes in oxidative stress levels in both plasma of presbycusis patients and mice. ⋯ In OC1 cells, METTL3 positively regulated SIRT1 protein levels, while reversely regulated the level of ROS and apoptosis. IGF2BP3 was found to be involved in the regulation of SIRT1 protein expression. In addition, METTL3 may play a protective role in oxidative stress-induced injury of OC1 cells, while both METTL3 and IGF2BP3 cooperatively regulate the level of m6A and the fate of SIRT1 mRNA in OC1 cells.