<oai_dc:dc xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:oai_dc="http://www.openarchives.org/OAI/2.0/oai_dc/" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xsi:schemaLocation="http://www.openarchives.org/OAI/2.0/oai_dc/ http://www.openarchives.org/OAI/2.0/oai_dc.xsd">
  <dc:creator>Eskes C</dc:creator>
  <dc:creator>Juillerat-Jeanneret L</dc:creator>
  <dc:creator>Leuba G</dc:creator>
  <dc:creator>Honegger P</dc:creator>
  <dc:creator>Monnet-Tschudi F</dc:creator>
  <dc:date>2003</dc:date>
  <dc:description xmlns:ns0="xml" ns0:lang="en">Trimethyltin (TMT) is a neurotoxicant known to induce early microglial activation. The present study was undertaken to investigate the role played by these microglial cells in the TMT-induced neurotoxicity. The effects of TMT were investigated in monolayer cultures of isolated microglia or in neuron-enriched cultures and in neuron-microglia and astrocyte-microglia cocultures. The end points used were morphological criteria; evaluation of cell death and cell proliferation; and measurements of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and nitric oxide (NO) release in culture supernatant. The results showed that, in cultures of microglia, TMT (10(-6) M) caused, after a 5-day treatment, an increased release of TNF-alpha, without affecting microglial shape or cell viability. When microglia were cocultured with astrocytes, TNF-alpha release was decreased to undetectable levels. In contrast, in neuron-microglia cocultures, TNF-alpha levels were found to increase at lower concentrations of TMT (i.e., 10(-8) M). Moreover, at 10(-6) M of TMT, microglia displayed further morphological activation, as suggested by process retraction and by decrease in cell size. No morphological activation was observed in cultures of isolated microglial cells and in astrocyte-microglia cocultures. With regard to neurons, 10(-6) M of TMT induced about 30% of cell death, when applied to neuron-enriched cultures, whereas close to 100% of neuronal death was observed in neuron-microglia cocultures. In conclusion, whereas astrocytes may rather dampen the microglial activation by decreasing microglial TNF-alpha production, neuronal-microglial interactions lead to enhanced microglial activation. This microglial activation, in turn, exacerbates the neurotoxic effects of TMT. TNF-alpha may play a major role in such cell-cell communications.</dc:description>
  <dc:identifier>https://sonar.ch/global/documents/189481</dc:identifier>
  <dc:language>eng</dc:language>
  <dc:relation>info:eu-repo/semantics/altIdentifier/doi/10.1002/jnr.10508</dc:relation>
  <dc:relation>info:eu-repo/semantics/altIdentifier/pmid/12548715</dc:relation>
  <dc:source>Journal of neuroscience research. - 2003</dc:source>
  <dc:subject xmlns:ns1="xml" ns1:lang="en">Animals</dc:subject>
  <dc:subject xmlns:ns2="xml" ns2:lang="en">Cell Communication</dc:subject>
  <dc:subject xmlns:ns3="xml" ns3:lang="en">Cells, Cultured</dc:subject>
  <dc:subject xmlns:ns4="xml" ns4:lang="en">Microglia</dc:subject>
  <dc:subject xmlns:ns5="xml" ns5:lang="en">Nerve Degeneration</dc:subject>
  <dc:subject xmlns:ns6="xml" ns6:lang="en">Neurons</dc:subject>
  <dc:subject xmlns:ns7="xml" ns7:lang="en">Rats</dc:subject>
  <dc:subject xmlns:ns8="xml" ns8:lang="en">Trimethyltin Compounds</dc:subject>
  <dc:subject xmlns:ns9="xml" ns9:lang="en">Tumor Necrosis Factor-alpha</dc:subject>
  <dc:title xmlns:ns10="xml" ns10:lang="en">Involvement of microglia-neuron interactions in the tumor necrosis factor-alpha release, microglial activation, and neurodegeneration induced by trimethyltin.</dc:title>
  <dc:type>http://purl.org/coar/resource_type/c_6501</dc:type>
</oai_dc:dc>