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Dorsal Spinal Cord (dorsal + spinal_cord)
Selected AbstractsExtracerebellar progenitors grafted to the neurogenic milieu of the postnatal rat cerebellum adapt to the host environment but fail to acquire cerebellar identitiesEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 8 2010Chiara Rolando Abstract Stem or progenitor cells acquire specific regional identities during early ontogenesis. Nonetheless, there is evidence that cells heterotopically transplanted to neurogenic regions of the developing or mature central nervous system may switch their fate to adopt host-specific phenotypes. Here, we isolated progenitor cells from different germinative sites along the neuraxis where GABAergic interneurons are produced (telencephalic subventricular zone, medial ganglionic eminence, ventral mesencephalon and dorsal spinal cord), and grafted them to the prospective white matter of the postnatal rat cerebellum, at the time when local interneurons are generated. The phenotype acquired by transplanted cells was assessed by different criteria, including expression of region-specific transcription factors, acquisition of morphological and neurochemical traits, and integration in the cerebellar cytoarchitecture. Regardless of their origin, all the different types of donor cells engrafted in the cerebellar parenchyma and developed mature neurons that shared some morphological and neurochemical features with local inhibitory interneurons, particularly in the deep nuclei. Nevertheless, transplanted cells failed to activate cerebellar-specific regulatory genes. In addition, their major structural features, the expression profiles of type-specific markers and the laminar placement in the recipient cortex did not match those of endogenous interneurons generated during the same developmental period. Therefore, although exogenous cells are influenced by the cerebellar milieu and show remarkable capabilities for adapting to the foreign environment, they essentially fail to switch their fate, integrate in the host neurogenic mechanisms and adopt clear-cut cerebellar identities. [source] Role of M2, M3, and M4 muscarinic receptor subtypes in the spinal cholinergic control of nociception revealed using siRNA in ratsJOURNAL OF NEUROCHEMISTRY, Issue 4 2009You-Qing Cai Abstract Muscarinic acetylcholine receptors (mAChRs) are involved in the control of nociception in the spinal cord. The M2, M3, and M4 mAChR subtypes are present in the spinal dorsal horn. However, the role of the individual subtypes in the anti-nociceptive effect produced by mAChR agonists is uncertain. Here, we determined the contribution of M2, M3, and M4 subtypes to spinal muscarinic analgesia by using small-interference RNA (siRNA) targeting specific mAChR subtypes in rats. The neuronal uptake and distribution of a chitosan-siRNA conjugated fluorescent dye in the spinal cord and dorsal root ganglion were confirmed after intrathecal injection. The control and gene-specific siRNA-chitosan complexes were injected intrathecally for three consecutive days. Quantitative reverse-transcription polymerase chain reaction analysis showed that treatment with siRNA targeting M2, M3, or M4 subtype produced a large reduction in the corresponding mRNA levels in the dorsal root ganglion and dorsal spinal cord. Also, the protein levels of the mAChR subtypes in the spinal cord were significantly down-regulated by siRNA treatment, as determined by the immunoprecipitation and receptor-binding assay. Treatment with the M2 -siRNA caused a large reduction in the inhibitory effect of muscarine on the nociceptive withdrawal threshold. Furthermore, M4 knockdown at the spinal level significantly reduced the anti-nociceptive effect of muscarine. However, the anti-nociceptive effect of muscarine was not significantly changed by the M3 -specific siRNA. Our study suggests that chitosan nanoparticles can be used for efficient delivery of siRNA into the neuronal tissues in vivo. Our findings also provide important functional evidence that M2 and M4, but not M3, contribute to nociceptive regulation by mAChRs at the spinal level. [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] Regulation of development of oligodendrocytesJOURNAL OF NEUROCHEMISTRY, Issue 2002K. Ikenaka Oligodendrocyte (OL) is the myelin-forming glial cell in the central nervous system. In the spinal cord, molecular markers for OL precursor cells (OPCs), such as PDGF a-receptor (PDGFR a), are first expressed in a strictly restricted focus of the ventral ventricular lumen at E12.5 in mouse and later spread throughout the cord. To investigate how they originate from these specific regions, we used an explant culture system of E12 mouse cervical spinal cord. When we cultured the ventral and dorsal spinal cords separately, a robust increase in the number of O4+ cells was observed in the ventral fragment. This phenomenon suggests the presence of factors inhibiting OL development from dorsal spinal cord. BMP4 is secreted from dorsal spinal cord and is a strong candidate for this factor; however, it did not affect OL development in our system. Here we show that Wnt-1 and Wnt-3a, in contrast, may have a role in OL maturation. The developmental profile of wnt-1/3a gene expressions in the dorsal spinal cord showed a significant correlation with that of the dorsal activity, which was very strong at E11, and then reduced to an undetectable level by E14. When Wnt-3a was added to the dissociation culture prepared from E14 mouse ventral cervical cords, the numbers of OL decreased. b-Catenin and LEF family proteins are known to form a transcription factor complex at the down stream of Wnt signalling. OL,like differentiation of CG4 cells was inhibited by constitutively active LEF-b-Catenin, supporting the idea that Wnt signalling directly inhibits OL differentiation. [source] | ||||||||||