Lack of neuroprotective effect of astroglia-derived BDNF on hippocampal cell cultures exposed to trimethyltin

• Autorzy: Figiel L. , Wlodarczyk J.
• Języki publikacji: EN

Abstrakty

EN

It is well known that in response to neuronal injury activated glial cells produce pro-infl ammatory cytokines and neurotrophic factors. These immunoregulatory molecules may play either neurotoxic or neuroprotective roles. In previous studies on mixed neuronal-glial cultures of rat hippocampal dentate gyrus we demonstrated that trimethyltin (TMT) induced neuronal cell death accompanied by an enhanced production of tumor necrosis factor alpha (TNF-α) in microglial cells and a strong increase in TNF-α receptor 1 (TNFR1) expression on astrocytes. Since evidence has been provided that TNFR1 could mediate the production of neurotrophic factors, in the current studies we examined whether the brain-derived neurotrophic factor (BDNF) is up-regulated after TMT exposure and whether it may exert neuroprotective effect on dentate granule cells. Using western blot analysis and immunocytochemical staining we have shown a dose-dependent increase in BDNF production, mainly in astrocytes. Quantitative fl uorescence analysis revealed that addition of anti-TNFR1 antibody to TMTtreated cultures suppresses the astroglial synthesis of BDNF. Nevertheless, immunocytochemical studies of active caspase-3 demonstrated the high level of its expression in cultures exposed to TMT, as well as in cultures pre-treated with BDNF. Our data suggest the involvement of TNFR1 pathway in BDNF production in astrocytes and indicate that this neurotrophic factor does not protect granule neurons against TMT injury.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2009
• Tom: 69
• Numer: 3
• Opis fizyczny: p.339

Twórcy

autor

Figiel L.

• Department of Molecular and Cellular Neurobiology, Nencki Institute of Experimental Biology Polish Academy of Sciences, Warsaw, Poland

autor

Wlodarczyk J.

• Department of Molecular and Cellular Neurobiology, Nencki Institute of Experimental Biology Polish Academy of Sciences, Warsaw, Poland