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Ventral Spinal Cord (ventral + spinal_cord)
Selected AbstractsDevelopmental characteristics of AMPA receptors in chick lumbar motoneuronsDEVELOPMENTAL NEUROBIOLOGY, Issue 11 2007Xianglian Ni Abstract Ca2+ fluxes through ionotropic glutamate receptors regulate a variety of developmental processes, including neurite outgrowth and naturally occurring cell death. In the CNS, NMDA receptors were originally thought to be the sole source of Ca2+ influx through glutamate receptors; however, AMPA receptors also allow a significant influx of Ca2+ ions. The Ca2+ permeability of AMPA receptors is regulated by the insertion of one or more edited GluR2 subunits. In this study, we tested the possibility that changes in GluR2 expression regulate the Ca2+ permeability of AMPA receptors during a critical period of neuronal development in chick lumbar motoneurons. GluR2 expression is absent between embryonic day (E) 5 and E7, but increases significantly by E8 in the chick ventral spinal cord. Increased GluR2 protein expression is correlated with parallel changes in GluR2 mRNA in the motoneuron pool. Electrophysiological recordings of kainate-evoked currents indicate a significant reduction in the Ca2+ -permeability of AMPA receptors between E6 and E11. Kainate-evoked currents were sensitive to the AMPA receptor blocker GYKI 52466. Application of AMPA or kainate generates a significant increase in the intracellular Ca2+ concentration in E6 spinal motoneurons, but generates a small response in older neurons. Changes in the Ca2+ -permeability of AMPA receptors are not mediated by age-dependent changes in the editing pattern of GluR2 subunits. These findings raise the possibility that Ca2+ influx through Ca2+ -permeable AMPA receptors plays an important role during early embryonic development in chick spinal motoneurons. © 2007 Wiley Periodicals, Inc. Develop Neurobiol, 2007 [source] Phenotype of V2-derived interneurons and their relationship to the axon guidance molecule EphA4 in the developing mouse spinal cordEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 11 2007Line Lundfald Abstract The ventral spinal cord consists of interneuron groups arising from distinct, genetically defined, progenitor domains along the dorsoventral axis. Many of these interneuron groups settle in the ventral spinal cord which, in mammals, contains the central pattern generator for locomotion. In order to better understand the locomotor networks, we have used different transgenic mice for anatomical characterization of one of these interneuron groups, called V2 interneurons. Neurons in this group are either V2a interneurons marked by the postmitotic expression of the transcription factor Chx10, or V2b interneurons which express the transcription factors Gata2 and Gata3. We found that all V2a and most V2b interneurons were ipsilaterally projecting in embryos as well as in newborns. V2a interneurons were for the most part glutamatergic while V2b interneurons were mainly GABAergic or glycinergic. Furthermore, we demonstrated that a large proportion of V2 interneurons expressed the axon guidance molecule EphA4, a molecule previously shown to be important for correct organization of locomotor networks. We also showed that V2 interneurons and motor neurons alone did not account for all EphA4-expressing neurons in the spinal cord. Together, these findings enable a better interpretation of neural networks underlying locomotion, and open up the search for as yet unknown components of the mammalian central pattern generator. [source] Dorsally derived BMP4 inhibits the induction of spinal cord oligodendrocyte precursorsJOURNAL OF NEUROCHEMISTRY, Issue 2002R. H. Miller During development oligodendrocyte precursors arise in a distinct domain of the ventral ventricular zone in the spinal cord that they share with motor neurons. The localized appearance of oligodendrocyte and motor neuron precursors is the result of local inductive signals including sonic hedgehog (Shh). Previous studies suggested that inhibitory signals from dorsal spinal cord act to sharpen the boundaries of the Shh induced region. Here we show that the dorsal spinal cord contains BMP4 during the developmental period when oligodendrocyte precursors first appear. In dissociated cultures of embryonic spinal cord cells, BMP4 competitively blocks the induction of oligodendrocyte precursors by Shh. Similarly, in embryonic slice preparations addition of BMP4 inhibited the appearance of oligodendrocyte precursors in the ventral spinal cord while addition of Shh enhanced their appearance. In vivo, transplantation of a BMP4 coated bead adjacent to the dorsal spinal cord inhibited ventral oligodendrogenesis while transplantation of a Shh coated bead enhanced ventral oligodendrogenesis. These data suggest that the initial localization of oligodendrocytes in the ventral spinal cord reflects the neutralization of dorsally-derived BMP4 inhibition by locally supplied Shh. [source] Immediate anti-tumor necrosis factor-, (etanercept) therapy enhances axonal regeneration after sciatic nerve crushJOURNAL OF NEUROSCIENCE RESEARCH, Issue 2 2010Kinshi Kato Abstract Peripheral nerve regeneration begins immediately after injury. Understanding the mechanisms by which early modulators of axonal degeneration regulate neurite outgrowth may affect the development of new strategies to promote nerve repair. Tumor necrosis factor-, (TNF-,) plays a crucial role in the initiation of degenerative cascades after peripheral nerve injury. Here we demonstrate using real-time Taqman quantitative RT-PCR that, during the time course (days 1,60) of sciatic nerve crush, TNF-, mRNA expression is induced at 1 day and returned to baseline at 5 days after injury in nerve and the corresponding dorsal root ganglia (DRG). Immediate therapy with the TNF-, antagonist etanercept (fusion protein of TNFRII and human IgG), administered systemically (i.p.) and locally (epineurially) after nerve crush injury, enhanced the rate of axonal regeneration, as determined by nerve pinch test and increased number of characteristic clusters of regenerating nerve fibers distal to nerve crush segments. These fibers were immunoreactive for growth associated protein-43 (GAP-43) and etanercept, detected by anti-human IgG immunofluorescence. Increased GAP-43 expression was found in the injured nerve and in the corresponding DRG and ventral spinal cord after systemic etanercept compared with vehicle treatments. This study established that immediate therapy with TNF-, antagonist supports axonal regeneration after peripheral nerve injury. © 2009 Wiley-Liss, Inc. [source] Postnatal phenotype and localization of spinal cord V1 derived interneuronsTHE JOURNAL OF COMPARATIVE NEUROLOGY, Issue 2 2005Francisco J. Alvarez Abstract Developmental studies identified four classes (V0, V1, V2, V3) of embryonic interneurons in the ventral spinal cord. Very little is known, however, about their adult phenotypes. Therefore, we characterized the location, neurotransmitter phenotype, calcium-buffering protein expression, and axon distributions of V1-derived neurons in the adult mouse spinal cord. In the mature (P20 and older) spinal cord, most V1-derived neurons are located in lateral LVII and in LIX, few in medial LVII, and none in LVIII. Approximately 40% express calbindin and/or parvalbumin, while few express calretinin. Of seven groups of ventral interneurons identified according to calcium-buffering protein expression, two groups (1 and 4) correspond with V1-derived neurons. Group 1 are Renshaw cells and intensely express calbindin and coexpress parvalbumin and calretinin. They represent 9% of the V1 population. Group 4 express only parvalbumin and represent 27% of V1-derived neurons. V1-derived Group 4 neurons receive contacts from primary sensory afferents and are therefore proprioceptive interneurons. The most ventral neurons in this group receive convergent calbindin-IR Renshaw cell inputs. This subgroup resembles Ia inhibitory interneurons (IaINs) and represents 13% of V1-derived neurons. Adult V1-interneuron axons target LIX and LVII and some enter the deep dorsal horn. V1 axons do not cross the midline. V1-derived axonal varicosities were mostly (>80%) glycinergic and a third were GABAergic. None were glutamatergic or cholinergic. In summary, V1 interneurons develop into ipsilaterally projecting, inhibitory interneurons that include Renshaw cells, Ia inhibitory interneurons, and other unidentified proprioceptive interneurons. J. Comp. Neurol. 493:177,192, 2005. © 2005 Wiley-Liss, Inc. [source] PGE2 receptors rescue motor neurons in a model of amyotrophic lateral sclerosisANNALS OF NEUROLOGY, Issue 2 2004Masako Bilak PhD Recent studies suggest that the inducible isoform of cyclooxygenase, COX-2, promotes motor neuron loss in rodent models of ALS. We investigated the effects of PGE2, a principal downstream prostaglandin product of COX-2 activity, on motor neuron survival in an organotypic culture model of ALS. We find that PGE2 paradoxically protects motor neurons at physiological concentrations in this model. PGE2 exerts its downstream effects by signaling through a class of four distinct G-protein,coupled E-prostanoid receptors (EP1,EP4) that have divergent effects on cAMP. EP2 and EP3 are dominantly expressed in ventral spinal cord in neurons and astrocytes, and activation of these receptor subtypes individually or in combination also rescued motor neurons. The EP2 receptor is positively coupled to cAMP, and its neuroprotection was mimicked by application of forskolin and blocked by inhibition of PKA, suggesting that its protective effect is mediated by downstream effects of cAMP. Conversely, the EP3 receptor is negatively coupled to cAMP, and its neuroprotective effect was blocked by pertussis toxin, suggesting that its protective effect is dependent on Gi-coupled heterotrimeric signaling. Taken together, these data demonstrate an unexpected neuroprotective effect mediated by PGE2, in which activation of its EP2 and EP3 receptors protected motor neurons from chronic glutamate toxicity. Ann Neurol 2004;56:240,248 [source] | ||||||||||