caa a22 4500 445376376 CHVBK 20180317143003.0 cr unu---uuuuu 170323e20110901xx s 000 0 eng 10.1007/s00702-011-0619-4 doi (NATIONALLICENCE)springer-10.1007/s00702-011-0619-4 Inhibition of phospholipase A2 in rat brain decreases the levels of total Tau protein [Elektronische Daten] [Evelin Schaeffer, Vanessa De-Paula, Emanuelle da Silva, Barbara de A. Novaes, Heni Skaf, Orestes Forlenza, Wagner Gattaz] The microtubule-associated protein Tau promotes the assembly and stability of microtubules in neuronal cells. Six Tau isoforms are expressed in adult human brain. All six isoforms become abnormally hyperphosphorylated and form neurofibrillary tangles in Alzheimer disease (AD) brains. In AD, reduced activity of phospholipase A2 (PLA2), specifically of calcium-dependent cytosolic PLA2 (cPLA2) and calcium-independent intracellular PLA2 (iPLA2), was reported in the cerebral cortex and hippocampus, which positively correlated with the density of neurofibrillary tangles. We previously demonstrated that treatment of cultured neurons with a dual cPLA2 and iPLA2 inhibitor, methyl arachidonyl fluorophosphonate (MAFP), decreased total Tau levels and increased Tau phosphorylation at Ser214 site. The aim of this study was to conduct a preliminary investigation into the effects of in vivo infusion of MAFP into rat brain on PLA2 activity and total Tau levels in the postmortem frontal cortex and dorsal hippocampus. PLA2 activity was measured by radioenzymatic assay and Tau levels were determined by Western blotting using the anti-Tau 6 isoforms antibody. MAFP significantly inhibited PLA2 activity in the frontal cortex and hippocampus. The reactivity to the antibody revealed three Tau protein bands with apparent molecular weight of close to 40, 43 and 46kDa in both brain areas. MAFP decreased the 46kDa band intensity in the frontal cortex, and the 43 and 46kDa band intensities in the hippocampus. The results indicate that in vivo PLA2 inhibition in rat brain decreases the levels of total (nonphosphorylated plus phosphorylated) Tau protein and corroborate our previous in vitro findings. Springer-Verlag, 2011 Phospholipase A2 nationallicence Tau protein nationallicence Frontal cortex nationallicence Hippocampus nationallicence Rat nationallicence Alzheimer disease nationallicence Schaeffer Evelin Laboratory of Neuroscience (LIM-27), Department and Institute of Psychiatry, Faculty of Medicine, University of São Paulo, Rua Dr. Ovídio Pires de Campos, 785, CEP 05403-010, São Paulo, SP, Brazil aut De-Paula Vanessa Laboratory of Neuroscience (LIM-27), Department and Institute of Psychiatry, Faculty of Medicine, University of São Paulo, Rua Dr. Ovídio Pires de Campos, 785, CEP 05403-010, São Paulo, SP, Brazil aut da Silva Emanuelle Laboratory of Neuroscience (LIM-27), Department and Institute of Psychiatry, Faculty of Medicine, University of São Paulo, Rua Dr. Ovídio Pires de Campos, 785, CEP 05403-010, São Paulo, SP, Brazil aut de A. Novaes Barbara Laboratory of Neuroscience (LIM-27), Department and Institute of Psychiatry, Faculty of Medicine, University of São Paulo, Rua Dr. Ovídio Pires de Campos, 785, CEP 05403-010, São Paulo, SP, Brazil aut Skaf Heni Laboratory of Neuroscience (LIM-27), Department and Institute of Psychiatry, Faculty of Medicine, University of São Paulo, Rua Dr. Ovídio Pires de Campos, 785, CEP 05403-010, São Paulo, SP, Brazil aut Forlenza Orestes Laboratory of Neuroscience (LIM-27), Department and Institute of Psychiatry, Faculty of Medicine, University of São Paulo, Rua Dr. Ovídio Pires de Campos, 785, CEP 05403-010, São Paulo, SP, Brazil aut Gattaz Wagner Laboratory of Neuroscience (LIM-27), Department and Institute of Psychiatry, Faculty of Medicine, University of São Paulo, Rua Dr. Ovídio Pires de Campos, 785, CEP 05403-010, São Paulo, SP, Brazil aut Journal of Neural Transmission Springer Vienna 118/9(2011-09-01), 1273-1279 0300-9564 118:9<1273 2011 118 702 https://doi.org/10.1007/s00702-011-0619-4 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00702-011-0619-4 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Schaeffer Evelin Laboratory of Neuroscience (LIM-27), Department and Institute of Psychiatry, Faculty of Medicine, University of São Paulo, Rua Dr. Ovídio Pires de Campos, 785, CEP 05403-010, São Paulo, SP, Brazil aut NATIONALLICENCE 700 1- De-Paula Vanessa Laboratory of Neuroscience (LIM-27), Department and Institute of Psychiatry, Faculty of Medicine, University of São Paulo, Rua Dr. Ovídio Pires de Campos, 785, CEP 05403-010, São Paulo, SP, Brazil aut NATIONALLICENCE 700 1- da Silva Emanuelle Laboratory of Neuroscience (LIM-27), Department and Institute of Psychiatry, Faculty of Medicine, University of São Paulo, Rua Dr. Ovídio Pires de Campos, 785, CEP 05403-010, São Paulo, SP, Brazil aut NATIONALLICENCE 700 1- de A. Novaes Barbara Laboratory of Neuroscience (LIM-27), Department and Institute of Psychiatry, Faculty of Medicine, University of São Paulo, Rua Dr. Ovídio Pires de Campos, 785, CEP 05403-010, São Paulo, SP, Brazil aut NATIONALLICENCE 700 1- Skaf Heni Laboratory of Neuroscience (LIM-27), Department and Institute of Psychiatry, Faculty of Medicine, University of São Paulo, Rua Dr. Ovídio Pires de Campos, 785, CEP 05403-010, São Paulo, SP, Brazil aut NATIONALLICENCE 700 1- Forlenza Orestes Laboratory of Neuroscience (LIM-27), Department and Institute of Psychiatry, Faculty of Medicine, University of São Paulo, Rua Dr. Ovídio Pires de Campos, 785, CEP 05403-010, São Paulo, SP, Brazil aut NATIONALLICENCE 700 1- Gattaz Wagner Laboratory of Neuroscience (LIM-27), Department and Institute of Psychiatry, Faculty of Medicine, University of São Paulo, Rua Dr. Ovídio Pires de Campos, 785, CEP 05403-010, São Paulo, SP, Brazil aut NATIONALLICENCE 773 0- Journal of Neural Transmission Springer Vienna 118/9(2011-09-01), 1273-1279 0300-9564 118:9<1273 2011 118 702 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer