Neuroscience
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Despite growing interest in meditation as a tool for alternative therapy of stress-related and psychosomatic diseases, brain mechanisms of beneficial influences of meditation practice on health and quality of life are still unclear. We propose that the key point is a persistent change in emotional functioning, specifically the modulation of the early appraisal of motivational significance of events. The main aim was to study the effects of long-term meditation practice on event-related brain potentials (ERPs) during affective picture viewing. ⋯ However, we found no differences in the long latency (400-800ms) responses to emotional images, associated with meditation practice. In addition we found stronger ERP negativity in the time window 200-300ms for meditators compared to the controls, regardless of picture valence. We assume that long-term meditation practice enhances frontal top-down control over fast automatic salience detection, based on amygdala functions.
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Caffeine, a methylated derivative of xanthine and widely consumed psychoactive substance, acts in several targets in the nervous system. We investigated its role in retinal explants of chick embryo analyzing the role of purinergic receptors in [(3)H]-GABA release induced by d-aspartate (d-asp). d-Asp increases GABA-release 4.5-fold when compared to basal levels from 13-day-old chick embryo retinal explants. Caffeine 500μM elevated d-asp-induced GABA release in 60%. ⋯ The GluN2B subunit-containing NMDAR antagonist ifenprodil inhibited the caffeine effect. Our results suggest that caffeine potentiates d-asp-induced GABA release, which is mediated by GAT-1, via inhibition of adenosine A1 receptor and activation of the PKA pathway. Regulation of NMDAR by phosphorylation of GluN2B subunit by a SFK may also be involved in the effect promoted by caffeine.
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Microglia, the primary immune cells in the brain, have been implicated as the predominant cells governing inflammation-mediated neuronal damage. In response to immunological challenges such as lipopolysaccharide (LPS), microglia are activated and subsequently inflammatory process is initiated as evidenced by the release of pro-inflammatory chemokines and cytokines. Here we show that Group I metabotropic glutamate receptor 5 (mGluR5) is involved in LPS-induced microglia activation. ⋯ LPS induced tumor necrosis factor-α (TNF-α) secretion in N9 microglia, but not in TLR4-mutant EOC 20 and TLR4-deficient primary mouse microglia. CHPG reduced LPS-caused TNF-α production, but MTEP increased LPS-induced TNF-α production and blocked the effect of CHPG in N9 microglia. These data demonstrate that mGluR5 and TLR4 are two critical receptors that mediate microglia activation in response to LPS, suggesting that mGluR5 may represent a novel target for modulating microglia-dependent neuroinflammation.
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Silent mating type information regulation 2 homolog 1 (SIRT1) is a class III histone deacetylase and activates peroxisome proliferator-activated receptor-γ co-activator-1α (PGC-1α) which attenuates oxidative damage. Alpha-lipoic acid (ALA) has been proven to protect the rat brain against cerebral ischemia injury by reducing oxidative stress. However, the underlying mechanisms are poorly understood. In this study, we investigated the potential neuroprotection and the possible role of ALA in SIRT1 pathway. ⋯ ALA protected the mouse brain against ischemic damage, and this protection may be through up-regulating SIRT1-dependent PGC-1α expression.
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Nitric oxide (NO) and oxidative stress caused by reactive oxygen species (ROS) accumulation are two important factors that lead to the progression of human neurological diseases. NO can be detrimental or protective to neurons under oxidative toxicity; however, in the case of brain exposure to oxidative stress, in addition to neurons, the existence of glia may also be disturbed by toxic ROS. The influence NO will have on ROS-mediated glial injury remains unclear. ⋯ H2O2 at toxic levels activated p38 mitogen-activated protein kinases (MAPK) and p53 pathways and increased DNA double strand breaks (DSBs) in microglia, whereas the rescue exerted by sublytic SNAP against toxic H2O2 occurred via the activation of both Akt and extracellular-signal-regulated kinase (ERK) cascades and decreased DNA DSBs. Moreover, a sublytic concentration of SNAP induced both heat shock protein 70 and heme oxygenase-1, which may be involved in decreasing the susceptibility of microglia to H2O2 toxicity. These results suggest that NO exhibits a concentration-dependent dual action of weakening or enhancing oxidative injury in mixed glia, particularly microglia.