http://www.cnr.it/ontology/cnr/individuo/prodotto/ID21206
GDNF selectively induces microglial activation and neuronal survival in CA1/CA3 hippocampal regions exposed to NMDA insult through Ret/ERK signalling. (Articolo in rivista)
- Type
- Label
- GDNF selectively induces microglial activation and neuronal survival in CA1/CA3 hippocampal regions exposed to NMDA insult through Ret/ERK signalling. (Articolo in rivista) (literal)
- Anno
- 2009-01-01T00:00:00+01:00 (literal)
- Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi
- 10.1371/journal.pone.0006486 (literal)
- Alternative label
- Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
- Boscia F; Esposito CL; Di Crisci A; de Franciscis V; Annunziato L; Cerchia L (literal)
- Rivista
- Note
- ISI Web of Science (WOS) (literal)
- Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
- Istituto per l'Endocrinologia e l'Oncologia Sperimentale del CNR ''G. Salvatore'' (literal)
- Titolo
- GDNF selectively induces microglial activation and neuronal survival in CA1/CA3 hippocampal regions exposed to NMDA insult through Ret/ERK signalling. (literal)
- Abstract
- The glial cell line-derived neurotrophic factor (GDNF) is a potent survival factor for several neuronal populations in different
brain regions, including the hippocampus. However, no information is available on the: (1) hippocampal subregions
involved in the GDNF-neuroprotective actions upon excitotoxicity, (2) identity of GDNF-responsive hippocampal cells, (3)
transduction pathways involved in the GDNF-mediated neuroprotection in the hippocampus. We addressed these
questions in organotypic hippocampal slices exposed to GDNF in presence of N-methyl-D-aspartate (NMDA) by
immunoblotting, immunohistochemistry, and confocal analysis. In hippocampal slices GDNF acts through the activation of
the tyrosine kinase receptor, Ret, without involving the NCAM-mediated pathway. Both Ret and ERK phosphorylation mainly
occurred in the CA3 region where the two activated proteins co-localized. GDNF protected in a greater extent CA3 rather
than CA1 following NMDA exposure. This neuroprotective effect targeted preferentially neurons, as assessed by NeuN
staining. GDNF neuroprotection was associated with a significant increase of Ret phosphorylation in both CA3 and CA1.
Interestingly, confocal images revealed that upon NMDA exposure, Ret activation occurred in microglial cells in the CA3 and
CA1 following GDNF exposure. Collectively, this study shows that CA3 and CA1 hippocampal regions are highly responsive
to GDNF-induced Ret activation and neuroprotection, and suggest that, upon excitotoxicity, such neuroprotection involves
a GDNF modulation of microglial cell activity (literal)
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