Neuroscience
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S100beta is a calcium-binding peptide produced mainly by astrocytes that exerts paracrine and autocrine effects on neurons and glia. We have previously shown that S100beta is markedly elevated at the mRNA level in the spinal cord following peripheral inflammation, intraplantar administration of complete Freund's adjuvant in the rat. The purpose of the present study was to further investigate the role of astrocytic S100beta in mediating behavioral hypersensitivity in rodent models of persistent pain. ⋯ S100beta genetically deficient mice displayed significantly increased tactile thresholds (reduced response to non-noxious stimuli) after nerve injury as compared with the wild type group. S100beta overexpressing mice displayed significantly decreased tactile threshold responses (enhanced response to non-noxious stimuli). Together, these results from both series of experiments using a peripheral nerve injury model in two different species implicate the involvement of glial-derived S100beta in the pathophysiology of neuropathic pain.
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The tripeptide, phenylalanine-glutamate-glycine (FEG) and its d-isomeric form phenylalanine-(D) glutamate-(D) glycine (feG), derived from submandibular gland peptide-T, significantly reduce the allergic inflammatory response and leukocyte trafficking and neutrophil migration into intestine, heart and lungs. Due to these actions, we hypothesized that feG would attenuate the early inflammatory response to spinal cord injury, reduce free radical production and improve neurological outcomes, like other leukocyte-limiting strategies we have used previously. We tested this using a clip compression model of spinal cord injury in rats. ⋯ Free radical production in the injured cord increased significantly after spinal cord injury and feG treatment significantly reduced this free radical production. Oxidative enzymes, lipid peroxidation and cell death were also significantly ( approximately 40%), gp91 ( approximately 30%), thiobarbituric acid reactive substance levels ( approximately 35%), 4-hydroxynonenal-bound protein ( approximately 35%) and caspase-3 ( approximately 32%). Early administration of feG decreases infiltration of inflammatory cells into the injured spinal cord and intraspinal free radical formation, thereby reducing oxidative damage and secondary cell death after spinal cord injury.
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Accumulating evidence suggests that a disruption of zinc (Zn) homeostasis may play a role in the pathogenesis of Alzheimer's disease. Although several Zn transporter proteins responsible for the regulation of Zn balance are present in the brain, there has been little study of these proteins in Alzheimer's disease. ⋯ Our results show that Zn transporter-4 and Zn transporter-6 are significantly (P<0.05) increased in hippocampus/parahippocampal gyrus of early Alzheimer's disease and Alzheimer's disease subjects. Zn transporter-6 is also increased (P<0.1) in the superior and middle temporal gyrus of Alzheimer's disease brain.
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Two volatile agents, isoflurane and sevoflurane have similar anesthetic properties but different potencies; this allows the discrimination between anesthetic potency and other properties on the protective mechanisms of volatile anesthesia. Two times the minimal alveolar concentration of an anesthetic is approximately the maximally used clinical concentration of that agent; this concentration is 2% for isoflurane and 4% for sevoflurane. We measured the effects of isoflurane and sevoflurane on cornus ammonis 1 (CA1) pyramidal cells in rat hippocampal slices subjected to 10 min of hypoxia (95% nitrogen 5% carbon dioxide) and 60 min of recovery. ⋯ If the same absolute concentration (4%) of isoflurane and sevoflurane is compared then the cellular changes during hypoxia are similar for both agents and they both improve recovery. We conclude that an anesthetic's absolute concentration and not its anesthetic potency correlates with improved recovery of CA1 pyramidal neurons. The mechanisms of sevoflurane-induced protection include delaying and attenuating the depolarization and the increase of cytosolic calcium and delaying the fall in ATP during hypoxia.
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Most gap junctions between neurons in mammalian retina contain abundant connexin36, often in association with the scaffolding protein zonula occludens-1. We now investigate co-association of connexin36, zonula occludens-1, zonula occludens-2 and Y-box transcription factor 3 (zonula occludens-1-associated nucleic acid-binding protein) in mouse and rat retina. By immunoblotting, zonula occludens-1-associated nucleic acid-binding protein and zonula occludens-2 were both detected in retina, and zonula occludens-2 in retina was found to co-immunoprecipitate with connexin36. ⋯ In addition, zonula occludens-1-associated nucleic acid-binding protein was abundant in a portion of ultrastructurally-defined gap junctions throughout the inner plexiform layer, and some of these junctions contained both connexin36 and zonula occludens-1-associated nucleic acid-binding protein. These distinct patterns of connexin36 association with zonula occludens-1, zonula occludens-2 and zonula occludens-1-associated nucleic acid-binding protein in different sublaminae of retina, and differential responses of these proteins to connexin36 gene deletion suggest differential regulatory and scaffolding roles of these gap junction accessory proteins. Further, the persistence of a subpopulation of zonula occludens-1/zonula occludens-2/zonula occludens-1-associated nucleic acid-binding protein co-localized puncta in the outer part of the inner plexiform layer of connexin36 knockout mice suggests close association of these proteins with other structures in retina, possibly including gap junctions composed of an as-yet-unidentified connexin.