title: Vasopressin protects hippocampal neurones in culture against nutrient deprivation or glutamate-induced apoptosis.
abstract: Vasopressin (VP) secreted within the brain modulates neuronal function by acting as a neurotransmitter. Recent studies show that VP prevents serum deprivation-induced apoptosis in the neuronal cell line, H32. To determine whether VP is anti-apoptotic in hippocampal neurones, primary cultures of these neurones were used to examine the effect of VP on neuronal culture supplement (B27) deprivation-, or glutamate-induced apoptosis, and the signalling pathways mediating the effects. Removal of B27 supplement from the culture medium for 24 h or the addition of glutamate (3-10μm) decreased neuronal viability (P<0.05) and increased Tdt-mediated dUTP nick-end labelling (TUNEL) staining and caspase-3 activity (P<0.05), which is consistent with apoptotic cell death. VP (10 nm) reduced B27 deprivation- or glutamate-induced cell death (P<0.05). These anti-apoptotic effects of VP were completely blocked by a V1 but not a V2 receptor antagonist, indicating that they are mediated via V1 VP receptors. The anti-apoptotic effect of VP in neurones involves activation of mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) and inositol trisphosphate/protein kinase B (Akt) signalling pathways. This was shown by the transient increases in phospho-ERK and phospho-Akt after incubation with VP revealed by western blot analyses, and the ability of specific inhibitors to reduce the inhibitory effect of VP on caspase-3 activity and TUNEL staining by 70% and 35%, respectively (P<0.05). These studies demonstrate that VP has anti-apoptotic actions in hippocampal neurones, an effect that is mediated by the MAPK/ERK and phosphatidylinositol-3 kinase/Akt signalling pathways. The ability of VP to reduce nutrient deprivation or glutamate overstimulation-induced neuronal death suggests that VP acts as a neuroprotective agent within the brain.
authors.affiliation: Developmental Endocrinology Branch, National Institute of Child Health and Human Development, NIH, Bethesda, MD, USA.
authors.forename: J
authors.initials: J
authors.lastname: Chen
authors.forename: G
authors.initials: G
authors.lastname: Aguilera
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free; D004791:Enzyme Inhibitors / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D005971:Glutamates / Q000494:pharmacology*; D006624:Hippocampus / Q000166:cytology*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology; D014667:Vasopressins / Q000494:pharmacology*
chemical_list: D016895:Culture Media, Serum-Free; D004791:Enzyme Inhibitors; D005971:Glutamates; D014667:Vasopressins; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D020928:Mitogen-Activated Protein Kinases