Neuroscience
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Systemic injection of lipopolysaccharide (LPS) induces a robust immune response as well as thermal and mechanical hyperalgesia. Spinal and peripheral glial cells have been implicated as important mediators in this hyperalgesia but the specific contributions of microglia versus astrocytes are not entirely clear. To better define these mechanisms, this study examined the febrile response, nociceptive sensitivity, glial cell reactivity and cytokine production in the dorsal root ganglion (DRG) and spinal cord in rats following systemic treatment with LPS and the effects of minocycline in countering these responses. ⋯ Minocycline suppressed all LPS-induced behavioral effects but not the febrile response. Moreover, minocycline prevented LPS-induced microglia/macrophage activation and cytokine responses in spinal cord and DRG, but did not affect the activation of astrocytes/satellite cells. These data demonstrate that LPS-induced changes in nociceptive sensitivity are likely mediated by activation of microglial cells and/or macrophages in the spinal cord and DRG.
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Valproic acid (VPA) is a short-chain branched fatty acid with anti-inflammatory, neuro-protective and axon remodeling effects. Here we have studied effects of VPA in gpMBP(68-84)-induced experimental autoimmune encephalomyelitis (EAE). Both preventive (from Day 0 to Day 18) and therapeutic (from Day 7 to Day 18 or from Day 9 to Day 19) VPA (500 mg/kg, intra-gastric) administration to EAE rats once daily greatly reduced the severity and duration of EAE, and suppressed mRNA levels of interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and IL-17, matrix metalloproteinase 9 (MMP9), inducible nitric oxide synthase (iNOS) and transcription factor T-bet, but increased levels of IL-4 mRNA in EAE spinal cords. ⋯ VPA treatment altered the cytokine milieu of lymph nodes, modulating the Th profile from Th1 and Th17 to a profile of Th2 and regulatory T cells. In addition, in vitro study showed that VPA inhibited non-specific lymphocyte proliferation in a dose-dependent manner. In summary, our data demonstrated that VPA could suppress systemic and local inflammation to improve outcome of EAE, suggesting that VPA might be a candidate for treatment of multiple sclerosis.
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Kainate receptors containing the GluK1 subunit (GluK1Rs; previously known as GluR5 kainate receptors) are concentrated in certain brain regions, where they play a prominent role in the regulation of neuronal excitability, by modulating GABAergic and/or glutamatergic synaptic transmission. In the basolateral nucleus of the amygdala (BLA), which plays a central role in anxiety as well as in seizure generation, GluK1Rs modulate GABAergic inhibition via postsynaptic and presynaptic mechanisms. However, the role of these receptors in the regulation of glutamate release, and the net effect of their activation on the excitability of the BLA network are not well understood. ⋯ Similar intra-BLA injections of UBP302 (20 nmol) had anxiolytic effects in the open field and the acoustic startle response tests, without affecting pre-pulse inhibition. These results suggest that although GluK1Rs in the rat BLA facilitate both GABA and glutamate release, the facilitation of glutamate release prevails, and these receptors can have an anxiogenic and seizurogenic net function. Presynaptic facilitation of glutamate release may, in part, underlie the hyperexcitability-promoting effects of GluK1R activation in the rat BLA.
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The aim of this study was to explore, during adolescence, alterations in the use of a sensori-motor representation as unveiled by the measurement of anticipatory postural control in a bimanual load-lifting task. We hypothesised that adolescence constitutes a period of refinement of anticipatory postural control due to on-going updates of the body schema and sensori-motor representations. The anticipatory postural control was assessed using a bimanual load-lifting paradigm in which subjects stabilise their left postural forearm, which is supporting an object, while they use their right hand to lift up the object. ⋯ The decrease of activity over postural flexors, which ensure postural stabilisation, appeared later in adolescents with respect to adults. Delayed timing adjustments and increased variability could reflect intense developmental processes underlain by an intense period of CNS maturation during adolescence. We discuss the role of brain maturation in the refinement of sensori-motor representations and the update of body schema.
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Accumulating evidence supports the hypothesis of ecstasy and amphetamine exhibiting neurotoxic properties in human recreational users. The extent and exact location of neuronal degeneration might also be associated with a specific profile of cognitive deterioration described in polydrug users. Voxel-based morphometry and cortical thickness analyses constantly gain attention for answering the question of associated neurological sequelae. ⋯ Our data support the hypothesis that massive recreational amphetamine-type stimulant polydrug use is associated with a thinning of cortical grey matter. Disrupted neuronal integrity in frontal regions does fit well into models of addiction and the cognitive deterioration in amphetamine-type stimulant polydrug users. The exact neurotoxic mechanisms of polydrug ecstasy and amphetamine use, however, remain speculative.