Neuroscience
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Alzheimer's disease (AD) has been considered as a metabolic dysfunction disease associated with impaired insulin signaling. Determining the mechanisms underlying insulin signaling dysfunction and resistance in AD will be important for its treatment. Impaired clearance of amyloid-β peptide (Aβ) significantly contributes to amyloid accumulation, which is typically observed in the brain of AD patients. ⋯ These results suggest that insulin exposure enhanced Aβ degradation via an increase in NEP secretion and IDE expression in astrocytes, via activation of the ERK-mediated pathway. The inhibition of insulin signaling pathways delayed Aβ degradation by attenuating alterations in NEP and IDE levels and competition with insulin and Aβ. Our results provide further insight into the pathological relevance of insulin resistance in AD development.
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Recent studies have demonstrated sexual dimorphisms in the mechanisms contributing to the development of chronic pain. Here we tested the hypothesis that microglia might preferentially regulate hyperalgesic priming in male mice. We based this hypothesis on evidence that microglia preferentially contribute to neuropathic pain in male mice via ionotropic purinergic receptor (P2XR) or p38 mitogen-activated protein kinase (p38) signaling. ⋯ Neither TNP-ATP nor skepinone could reverse priming once it had already been established in male mice suggesting that these pathways must be inhibited early in the development of hyperalgesic priming to have an effect. Our work is consistent with previous findings that P2XR and p38 inhibition can lead to male-specific effects on pain behaviors in mice. However, given that we did not observe microglial activation at time points where these drugs were effective, our work also questions whether these effects can be completely attributed to microglia.
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Interleukin-33 (IL-33), a novel member of the IL-1 family, expressed in many tissue and cell types, is involved in inflammation and immune functions. Previous studies suggest that IL-33 may play a role in ischemic stroke. Here, we evaluated the effect of IL-33 in cerebral ischemia-reperfusion-induced injury and investigated its underlying mechanism. ⋯ IL-33 deficiency led to more biased to M2-like activities. The aggravated cerebral ischemia-reperfusion injury in IL-33-deficient mice is partially restored by intracerebroventricular injection of IL-33. These data suggest that IL-33 promotes the amplification of macrophage polarization and cytokine production associated with M2 macrophage-like microglial immune phenotype, which may contribute to the protective effects in the ischemic stroke, and that IL-33 may be a potential therapeutic target for ischemic stroke.
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Thiamine deficiency (TD) has been used as an experimental model in rodents to study the molecular mechanisms of neurodegeneration and its association with behavioral changes. The aims of the present study were to investigate the spatial cognitive performance of pyrithiamine-induced thiamine deficiency (PTD) in adult male rats and disclose the thalamic proteome alterations caused by a severe TD episode. After the onset of the neurological signs, such as seizure and/or loss of righting reflex, the TD treatment was interrupted. ⋯ These could explain the outcome in neurotransmitter release changes caused by TD, previously observed by our group and by other authors. These findings disclose the role of key proteins and metabolic pathways probably involved in the neurodegeneration process induced by TD. These proteins represent relevant molecular targets for future studies focusing also on the molecular basis of selective vulnerability of some brain areas to TD insult.
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During mobile phone conversations, the temporal lobe neural networks involved in processing auditory information are exposed to electromagnetic fields (EMF) such as pulse-modulated GSM-1800 MHz radiofrequencies that convey wireless communications. The effects of these EMF on the brain affected by a pathological condition remain little investigated. In this study, rats injected with lipopolysaccharide (LPS) to induce neuroinflammation were exposed "head-only" to GSM-1800 MHz signals for two hours at a specific absorption rate (SAR) that reached an average value of 1.55 W/kg in the auditory cortex (ACx). ⋯ The response latency and the bandwidth of the frequency tuning were unchanged, but the GSM exposure led to a higher proportion of cortical sites exhibiting abnormally high acoustic thresholds. These modifications were not observed in rats exposed to GSM-1800 MHz without pretreatment with LPS. Together our data provide evidence that in neuroinflammatory conditions, acute exposure to GSM-1800 MHz can significantly affect microglia and neuronal activity underling auditory perception.