gdnf selectively induces microglial activation and neuronal survival in ca1ca3 hippocampal regions exposed to nmda insult through reterk signallinggdnf选择性地诱导小胶质激活和神经元生存ca1ca3海马区域暴露通过reterk信号门冬氨酸侮辱.pdfVIP

GDNF Selectively Induces Microglial Activation and Neuronal Survival in CA1/CA3 Hippocampal Regions Exposed to NMDA Insult through Ret/ERK Signalling 1 2 1 2 Francesca Boscia , Carla Lucia Esposito , Antonella Di Crisci , Vittorio de Franciscis , 1 2 Lucio Annunziato *, Laura Cerchia * ` ` 1 Dipartimento di Neuroscienze, Sezione di Farmacologia, Facolta di Medicina e Chirurgia, Universita degli Studi di Napoli ‘‘Federico II’’, Naples, Italy, 2 Istituto per l’Endocrinologia e l’Oncologia Sperimentale del CNR ‘‘G. Salvatore’’, Naples, Italy 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 NM