Involvement of proBDNF in neuronal cell death induced by trimethyltin

• Autorzy: Figiel I.
• Języki publikacji: EN

Abstrakty

EN

It is well established that in response to neuronal injury glial cells produce various pro-inflammatory cytokines and neurotrophic factors. These immunoregulatory molecules have been shown to play an important role in sustaining and modulating neurodegenerative events or to promote cell survival. To address question about molecular mechanisms of interactions between neurons and glial cells in pathogenic conditions, we used the in vitro model of mixed neuronal-glial cultures of rat hippocampal dentate gyrus treated with trimethyltin (TMT). In previous studies we demonstrated that TMT induced neuronal apoptosis, which was accompanied by an enhanced production of tumor necrosis factor (TNF-α) in microglial cells and a strong increase in brain-derived neurotrophic factor (BDNF) expression in astrocytes. Since evidence has been provided that BDNF exerts growth promoting actions on hippocampal dentate granule neurons and is implicated in resistance of these cells to various insults, the current study was dedicated to elucidate whether BDNF may promote beneficial effect on TMT-injured dentate neurons. Immunocytochemical studies of active caspase-3 expression revealed that pretreatment of the cultures with recombinant BDNF did not diminish neuronal injury. On the other hand, using western blot analysis it was demonstrated that TMT evoked increased expression of proBDNF (32 kDa) as well as p75 neurotrophin receptor (p75NTR). Moreover, addition of anti-p75NTR neutralizing antibody to the cultures suppressed TMT-induced apoptosis. These results indicate that neither endogenous nor exogenous BDNF is able to provide neurotrophic support for TMT-injured dentate granule neurons and suggest potential deleterious effect of proBDNF in this model of neurodegeneration.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2011
• Tom: 71
• Numer: 1
• Opis fizyczny: p.175

Twórcy

autor

Figiel I.

• Nencki Institute of Experimental Biology Polish Academy of Sciences, Warsaw, Poland