Selective injury to dopaminergic neurons up-regulates GDNF in substantia nigra postnatal cell cultures: Role of neuron–glia crosstalk

Autor: Ana Saavedra, Graça Baltazar, Paulo Santos, Caetana M. Carvalho, Emília P. Duarte
Jazyk: angličtina
Rok vydání: 2006
Předmět:
Zdroj: Neurobiology of Disease, Vol 23, Iss 3, Pp 533-542 (2006)
Druh dokumentu: article
ISSN: 1095-953X
DOI: 10.1016/j.nbd.2006.04.008
Popis: The effect of selective injury to dopaminergic neurons on the expression of glial cell line-derived neurotrophic factor (GDNF) was examined in substantia nigra cell cultures. H2O2, mimicking increased oxidative stress, or l-DOPA, the main symptomatic treatment for Parkinson's disease, increased GDNF mRNA and protein levels in a time-dependent mode in neuron–glia mixed cultures. The concentration dependence indicated that mild, but not extensive, injury induced GDNF up-regulation. GDNF neutralization with an antibody decreased dopaminergic cell viability in H2O2-treated cultures, showing that up-regulation of GDNF was protecting dopaminergic neurons. Neither H2O2 nor l-DOPA directly affected GDNF expression in astrocyte cultures, but conditioned media from challenged mixed cultures increased GDNF mRNA and protein levels in astrocyte cultures, indicating that GDNF up-regulation was mediated by neuronal factors. Since pretreatment with 6-OHDA completely abolished H2O2-induced GDNF up-regulation, we propose that GDNF up-regulation is triggered by failing dopaminergic neurons that signal astrocytes to increase GDNF expression.
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