Neuroscience
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The main goal of this paper is to introduce the concept of iso-perceptual manifold for perception of body configuration and related variables (kinesthetic perception) and to discuss its relation to the equilibrium-point hypothesis and the concepts of reference coordinate and uncontrolled manifold. Hierarchical control of action is postulated with abundant transformations between sets of spatial reference coordinates for salient effectors at different levels. ⋯ Some combinations of afferent and efferent signals, in particular those implying a violation of body's integrity, give rise to variable percepts by artificial projection onto iso-perceptual manifolds. This framework is used to interpret unusual features of vibration-induced kinesthetic illusions and to predict new illusions not yet reported in the literature.
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Aromatase is a key enzyme responsible for the biosynthesis of estrogen from testosterone. Although recent evidence indicates that spinal cord aromatase participates in nociceptive processing, the mechanisms underlying its regulation and its involvement in nociception remain unclear. The present study focuses on the potential role of astrocyte aromatase in formalin-induced acute pain and begins to uncover one mechanism by which spinal aromatase activation is controlled. ⋯ BD1047 blocked the dephosphorylation of aromatase and potentiated the pharmacological effect of letrozole on formalin-induced nociceptive responses. In addition, i.t. administration of a sub-effective dose of BD1047 potentiated the pharmacological effect of cyclosporin A (a calcineurin inhibitor) on both the formalin-induced reduction in phospho-serine levels of aromatase and nociceptive behavior. These results suggest that dephosphorylation is an important regulatory mechanism involved in the rapid activation of aromatase and that spinal sigma-1 receptors mediate this dephosphorylation of aromatase through an intrinsic calcineurin pathway.
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Understanding neuroadaptations involved in obesity is critical for developing new approaches to treatment. Diet-induced neuroadaptations within the dorsal striatum have the capacity to drive excessive food seeking and consumption. Five-week-old C57BL/6J mice consumed a high-fat, high-sugar 'western diet' (WD) or a control 'standard diet' (SD) for 16 weeks. ⋯ Neuronal excitability and GABAergic transmission were unaffected by diet in either striatal subregion. Our results demonstrate that a high-fat, high-sugar diet alters facets of glutamate, dopamine, and opioid signaling within the dorsal striatum, with some subregion specificity. These alterations within a brain area known to play a role in food motivation/consumption and habitual behavior are highly relevant for the clinical condition of obesity and its treatment.
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Both spinal cord infiltrating CD4+ T lymphocytes and microglial CD40 contribute to the maintenance of neuropathic pain-like behaviors induced by spinal nerve L5 transection (L5Tx), a murine model of neuropathic pain. Here, we sought to investigate the involvement of multiple chemokines in microglial CD40-mediated and CD4+ T lymphocytes-mediated L5Tx-induced sensory hypersensitivity. Spinal cord chemokine expression in CD4 knockout (KO), CD40 KO, and wild type (WT) BALB/c mice was determined at the protein level via multiplex assays and at the RNA level via quantitative real-time PCR. ⋯ Intrathecal administration of CXCL1 in WT mice significantly reduced L5Tx-induced mechanical hypersensitivity. CD40 KO mice also displayed higher levels of Ly6G (neutrophil marker) RNA expression in the lumbar spinal cord post-L5Tx. Altogether, our data suggest that CD4+ T lymphocytes and microglial CD40 mediate their pro-nociceptive effects in part by promoting selected chemokine responses, and more importantly, CXCL1 can play an anti-nociceptive role in peripheral nerve injury-induced neuropathic pain, which is possibly mediated by infiltrating neutrophils.