Project description:Analysis of the effects of three members of the FGF family (FGF1, FGF2 and FGF9) and bone morphogenic protein 4 (BMP4) on myelinating cultures generated from dissociated embryonic spinal cord. The results of both immediate (24 hours, T1 (24 hrs)) and long term treatments (10days, T2) give insights into the cumulative effects of sustained FGF and BMP mediated signal transduction in the pathogenesis of demyelinating diseases. Dissociated myelinating cultures were generated from neurosphere derived astrocytes (generated from striata of P1 Sprague-Dawley rats) and spinal cord cells from E15.5 Sprague-Dawley(SD) embryos. The effect of recombinant human FGF9 and other soluble factors on these in vitro myelinating cultures was investigated by adding them to the culture media after 18 days in vitro (DIV). The effects of each factor were analysed using three independent cultures at two time points (19DIV and 28 DIV).
Project description:Analysis of the effects of three members of the FGF family (FGF1, FGF2 and FGF9) and bone morphogenic protein 4 (BMP4) on myelinating cultures generated from dissociated embryonic spinal cord. The results of both immediate (24 hours, T1 (24 hrs)) and long term treatments (10days, T2) give insights into the cumulative effects of sustained FGF and BMP mediated signal transduction in the pathogenesis of demyelinating diseases.
Project description:Analysis of the effects of different FGF2 variants (human FGFs-hFGF2, wild-type protein and N-terminal truncated FGF2-F2V2) on myelinating cultures generated from dissociated embryonic spinal cord after 24 hours treatment to give insights into the effects of the N-terminal region of FGF2 on FGF signalling and its implications in demyelinating diseases.
Project description:Analysis of the effects of sulphatide specific antibody (O4, 20microg/ml) on myelinating cultures generated from dissociated embryonic rat spinal cord after 24 hours treatment to give insights into effects of lipid-specific antibodies and its implication in demyelinating diseases.
Project description:Failure of remyelination in multiple sclerosis (MS) is associated with inhibition of oligodendrocyte precursor (OPC) differentiation, but the cellular and molecular mechanisms involved remain poorly understood. We now report inflammatory demyelination in MS is associated with localized expression of fibroblast growth factor 9 (FGF9) by oligodendrocytes and to a lesser extent astrocytes, and demonstrate FGF9 inhibits myelination and remyelination in vitro. This inhibitory activity is reversible and due to an off target FGF9-dependent effect on astrocytes that disrupts in the growth factor milieu required to support myelination. We identify multiple downstream events induced by FGF9 associated with this effect including increased expression of leukaemia inhibitory growth factor (LIF) and FGF2, both of which are shown to inhibit myelination if present in excess. These studies identify FGF9-dependent signal transduction in astrocytes as a novel target for therapeutic strategies designed to enhance remyelination by endogenous OPC in MS. Gene expression profiles of rat myelinating cultures grown in the presence or absence of FGF9 (100 ng/ml) for 24h and 10 days were generated using Affymetrix GeneChip® Rat Gene 1.0 ST Arrays. Each time point (T1: 24 hrs, and T2: 10 days) has Control (CTR) and Treatment (FGF) groups, with two replicates in each group. In total, 8 arrays were generated from the four groups (CTR-T1, CTR-T2, FGF-T1 and FGF-T2).
Project description:Few studies have assessed the patterns of parasite populations of rodents over a longitudinal gradient in Chile. In this work, the gastrointestinal helminthic fauna of invasive rodents in Chile was examined to assess the association between their presence/absence and abundance with latitude, host sex, and host body condition, and to assess the coexistence and correlation of the abundance between parasite species. Rodents were obtained from 20 localities between 33 and 43°S. Helminths were extracted from the gastrointestinal tract and identified morphologically. Overall, 13 helminth taxa were obtained. The most frequently identified parasite species was Heterakis spumosa, and the most abundant was Syphacia muris, while Physaloptera sp. was the most widely distributed. No locality presented with a coexistence that was different from that expected by chance, while the abundance of five helminthic species correlated with the abundance of another in at least one locality, most likely due to co-infection rather than interaction. Host sex was associated with parasite presence or abundance, and female sex-biased parasitism was notably observed in all cases. Body condition and latitude presented either a positive or negative association with the presence or abundance of parasites depending on the species. It is notable that the likely native Physaloptera sp. is widely distributed among invasive rodents. Further, gravid females were found, suggesting spillback of this species to the native fauna. The low frequency and abundance of highly zoonotic hymenolepid species suggest that rodents are of low concern regarding gastrointestinal zoonotic helminths.