We report Nogo-A as an oligodendroglial component congregating and interacting with the Caspr±F3 complex at paranodes. However, its receptor Nogo-66 receptor (NgR) does not segregate to speci®c axonal domains. CHO cells cotransfected with Caspr and F3, but not with F3 alone, bound speci®cally to substrates coated with Nogo-66 peptide and GST±Nogo-66. Binding persisted even after phosphatidylinositolspeci®c phospholipase C (PI-PLC) removal of GPIlinked F3 from the cell surface, suggesting a direct interaction between Nogo-66 and Caspr. Both Nogo-A and Caspr co-immunoprecipitated with Kv1.1 and Kv1.2, and the developmental expression pattern of both paralleled compared with Kv1.1, implicating a transient interaction between Nogo-A±Caspr and K + channels at early stages of myelination. In pathological models that display paranodal junctional defects (EAE rats, and Shiverer and CGT ±/± mice), distances between the paired labeling of K + channels were shortened signi®cantly and their localization shifted toward paranodes, while paranodal Nogo-A congregation was markedly reduced. Our results demonstrate that Nogo-A interacts in trans with axonal Caspr at CNS paranodes, an interaction that may have a role in modulating axon±glial junction architecture and possibly K + -channel localization during development.
Background: Function of Dhrs3 and importance of the upstream metabolism of retinoic acid are not well understood in early embryonic development. Results: Dhrs3 attenuates retinoic acid synthesis and is required for embryonic patterning. Conclusion: dhrs3 is involved in maintaining balance of retinoic acid signaling and therefore regulates body axis formation. Significance: This is the first functional study of Xenopus dhrs3 in embryonic development.
Glioma is the most common primary intracranial malignant tumor. Despite advances in surgical techniques and adjuvant radio- and chemotherapies, the prognosis for patients with glioma remains poor. We have explored the effects of using genetically modified mesenchymal stem cells (MSCs) to treat malignant glioma in rats. Mesenchymal stem cells isolated from Sprague-Dawley rats can directly suppress the growth of C6 cells in vitro. MSCs transplanted intratumorally can also significantly inhibit the growth of glioma and prolong survival in C6 glioma-bearing models. MSCs producing Interleukin-18 infected by adenoviral vector inhibited glioma growth and prolonged the survival of glioma-bearing rats. Transplantation of IL-18 secreting MSCs was associated with enhanced T cell infiltration and long-term anti-tumor immunity. Thus, IL-18 may be an effective adoptive immunotherapy for malignant glioma. When used in conjunction with MSCs as targeting vehicles in vivo, IL-18 may offer a promising new treatment option for malignant glioma.
Autografts have been extensively studied to facilitate optic nerve (ON) regeneration in animal experiments, but the clinical application of this approach to aid autoregeneration has not yet been attempted. This study aims to explore the guided regeneration by an artificial polyglycolic acid-chitosan conduit coated with recombinant L1-Fc. Consistent with previous studies; in vitro assay showed that both chitosan, a natural biomaterial, and the neural cell adhesion molecule L1-Fc enhanced neurite outgrowth. Rat optic nerve transection was used as an in vivo model. The implanted PGA-chitosan conduit was progressively degraded and absorbed, accompanied by significant axonal regeneration as revealed by immunohistochemistry, anterograde and retrograde tracing. The polyglycolic acid-chitosan conduit coated with L1-Fc showed more effective to promote axonal regeneration and remyelination. Taken together, our observations demonstrated that the L1-Fc coated PGA-chitosan conduits provided a compatible and supportive canal to guild the injured nerve regeneration and remyelination.
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