Neuroscience
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Seizures increase the synthesis of brain-derived neurotrophic factor in forebrain areas, suggesting this neurotrophin has biological actions in epileptic tissue. The understanding of these actions requires information on the sites and extent of brain-derived neurotrophic factor production in areas involved in seizures onset and their spread. In this study, we investigated by immunocytochemistry the changes in brain-derived neurotrophic factor in the hippocampus, entorhinal and perirhinal cortices of rats at increasing times after acute seizures eventually leading to spontaneous convulsions. ⋯ In the dentate gyrus, changes in immunoreactivity depended on sprouting of mossy fibres as assessed by growth-associated protein-43-immunoreactivity. These modifications were inhibited by repeated anticonvulsant treatment with phenobarbital. The dynamic and temporally-linked alterations in brain-derived neurotrophic factor and neuropeptide Y in brain regions critically involved in epileptogenesis suggest a functional link between these two substances in the regulation of network excitability.
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The present studies used anatomical tract-tracing techniques to delineate the organization of pathways linking the medial preoptic area and the ventral medulla, two key regions involved in neuroendocrine, autonomic and sensory regulation. Wheatgerm agglutinin-horseradish peroxidase injections into the ventromedial medulla retrogradely labeled a large number of neurons in the medial preoptic area, including both the median and medial preoptic nuclei. The termination pattern of preoptic projections to the medulla was mapped using the anterograde tracers Phaseolus vulgaris leucoagglutinin and biotinylated dextran amine. ⋯ The present findings suggest that the medial preoptic area and ventral midline raphe nuclei share reciprocal connections that are organized in a highly symmetrical fashion. By contrast, preoptic-lateral medullary pathways are not reciprocal. These preoptic-brainstem circuits may participate in antinociceptive, autonomic and reproductive behaviors.
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Sprouting of the mossy fiber axons of the dentate granule cells is a structural neuronal plasticity found in the mature brain of epileptic humans and experimental animals. Mossy fiber sprouting typically arises in experimental animals after repeated seizures and may contribute to the hyperexcitability of the epileptic brain. Investigation of the molecular triggers and spatial cues involved in mossy fiber sprouting has been hampered by the lack of an optimal in vitro model for studying this rearrangement. ⋯ The cellular and molecular determinants required for kainic acid-induced cell death and subsequent mossy fiber reorganization thus appear to be intrinsic to the hippocampal slice preparation, and are preserved in culture. Given the ease with which functional inhibitors or pharmacological agents may be utilized in this system, slice cultures may provide a powerful model in which to study the molecular components involved in triggering mossy fiber outgrowth and underlying its laminar specificity. Elucidation of these molecular pathways will likely have both specific utility in clarifying the functional consequences of mossy fiber sprouting, as well as general utility in understanding of synaptic reorganization in the mature central nervous system.
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The expression of galanin and neuropeptide Y in rat lumbar 5 (L5) dorsal root ganglia and dorsal horn (L4-5) was studied after four types of peripheral nerve injury using immunohistochemistry and in situ hybridization. The possible correlation between these two peptides and tactile allodynia-like behaviour was analysed as well. The models employed were the Gazelius (photochemical lesion) and Seltzer and Bennett (constriction lesions) models, as well as complete sciatic nerve transection (axotomy). ⋯ Furthermore, an increase in galanin-immunoreactive fibres was found in the superficial laminae of the ipsilateral dorsal horn in all lesion models, especially in lamina II. A dramatic increase in the number of neuropeptide Y and neuropeptide Y messenger RNA-positive neuron profiles was also found in the ipsilateral dorsal root ganglia in all models, but no significant difference was found in peptide levels between allodynic and non-allodynic rats in any of the models. The present results suggest that the levels of endogenous galanin may play a role in whether or not allodynia develops in the Bennett model.
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Bovine SCO-spondin was shown to be a brain-secreted glycoprotein specifically expressed in the subcommissural organ, an ependymal differentiation located in the roof of the Sylvian aqueduct. Also, SCO-spondin makes part of Reissner's fiber, a phylogenetically and ontogenetically conserved structure present in the central canal of the spinal cord of chordates. This secretion is a large multidomain protein probably involved in axonal growth and/or guidance. ⋯ In addition, conserved glycoproteins present in the subcommissural organ and Reissner's fiber were revealed by immunohistochemistry using antibodies raised against bovine Reissner's fiber. Variation in the sites of Reissner's fiber production according to chordate subphylum, presence of this structure in the spinal cord, and conservation of the SCO-spondin gene are discussed in the context of chordate central nervous system development. These results indicate that SCO-spondin is an ancient ependymal secretion, making part of Reissner's fiber, that may have had an important function during the evolution of the central nervous system in chordates, including that of the spinal cord.