title: Inhibition of phospholipase A2 reduces neurite outgrowth and neuronal viability.
abstract: Phospholipase A2 (PLA(2)) has been implicated in neurodevelopmental processes and in the early development of the nervous system. We investigated the effects of the inhibition of calcium-dependent and calcium-independent subtypes of cytosolic PLA2 (cPLA2 and iPLA2) on the development and viability of primary cultures of cortical and hippocampal neurons. PLA2 in these cultures was continuously inhibited with methylarachidonyl-fluorophosphonate (MAFP), an irreversible inhibitor of cPLA2 and iPLA2, or with bromoenol lactone (BEL), an irreversible selective iPLA2 inhibitor. The effect of PLA2 inhibitors on the development of neuronal cultures was ascertained by total cell count and morphological characterisation. Neuronal viability was quantified with MTT assays. Inhibition of PLA2 resulted in reduction of neuritogenesis and neuronal viability, disrupting neuronal homeostasis and leading to neuronal death. We conclude that the functional integrity of both calcium-dependent and calcium-independent cytosolic PLA2 is necessary for the in vitro development of cortical and hippocampal neurons.
authors.affiliation: Laboratory of Neuroscience (LIM-27), Department and Institute of Psychiatry, Faculty of Medicine, University of Sao Paulo, Rua Dr. Ovídio Pires de Campos s/n, 05403-010 Sao Paulo, Brazil. forlenza@usp.br
authors.forename: Orestes V
authors.initials: OV
authors.lastname: Forlenza
authors.forename: Camila T
authors.initials: CT
authors.lastname: Mendes
authors.forename: Suely K N
authors.initials: SK
authors.lastname: Marie
authors.forename: Wagner F
authors.initials: WF
authors.lastname: Gattaz
mesh_terms: D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000196:embryology; D054522:Group VI Phospholipases A2; D006624:Hippocampus / Q000196:embryology; D009281:Naphthalenes / Q000494:pharmacology*; D016501:Neurites / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000166:cytology* / Q000187:drug effects; D063065:Organophosphonates / Q000494:pharmacology*; D010741:Phospholipases A / Q000037:antagonists & inhibitors*; D054467:Phospholipases A2; D011753:Pyrones / Q000494:pharmacology*; D051381:Rats
chemical_list: D001095:Arachidonic Acids; D009281:Naphthalenes; D063065:Organophosphonates; D011753:Pyrones; C104810:methyl arachidonylfluorophosphonate; C068314:6-(bromomethylene)tetrahydro-3-(1-naphthaleneyl)-2H-pyran-2-one; D010741:Phospholipases A; D054522:Group VI Phospholipases A2; D054467:Phospholipases A2