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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Inhibition of phospholipase A(2) in rat brain decreases the levels of total Tau protein

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Author(s):
Schaeffer, Evelin L. [1, 2] ; De-Paula, Vanessa J. [1, 2] ; da Silva, Emanuelle R. [1, 2] ; Novaes, Barbara de A. [1, 2] ; Skaf, Heni D. [1, 2] ; Forlenza, Orestes V. [1, 2] ; Gattaz, Wagner F. [1, 2]
Total Authors: 7
Affiliation:
[1] Univ Sao Paulo, Fac Med, Dept Psychiat, Lab Neurosci LIM 27, BR-05403010 Sao Paulo - Brazil
[2] Univ Sao Paulo, Fac Med, Inst Psychiat, Lab Neurosci LIM 27, BR-05403010 Sao Paulo - Brazil
Total Affiliations: 2
Document type: Journal article
Source: JOURNAL OF NEURAL TRANSMISSION; v. 118, n. 9, p. 1273-1279, SEP 2011.
Web of Science Citations: 15
Abstract

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 A(2) (PLA(2)), specifically of calcium-dependent cytosolic PLA(2) (cPLA(2)) and calcium-independent intracellular PLA(2) (iPLA(2)), 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 cPLA(2) and iPLA(2) inhibitor, methyl arachidonyl fluorophosphonate (MAFP), decreased total Tau levels and increased Tau phosphorylation at Ser(214) 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 PLA(2) activity and total Tau levels in the postmortem frontal cortex and dorsal hippocampus. PLA(2) activity was measured by radioenzymatic assay and Tau levels were determined by Western blotting using the anti-Tau 6 isoforms antibody. MAFP significantly inhibited PLA(2) 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 46 kDa in both brain areas. MAFP decreased the 46 kDa band intensity in the frontal cortex, and the 43 and 46 kDa band intensities in the hippocampus. The results indicate that in vivo PLA(2) inhibition in rat brain decreases the levels of total (nonphosphorylated plus phosphorylated) Tau protein and corroborate our previous in vitro findings. (AU)

FAPESP's process: 04/14516-0 - Phospholipase A2 inhibition in the hippocampus of mice and their differential effects on the free flow of plasma and nuclear membranes: are there any possible correlations with memory?
Grantee:Wagner Farid Gattaz
Support Opportunities: Regular Research Grants
FAPESP's process: 02/13633-7 - Phospholipid metabolism in neuropsychiatric disorders
Grantee:Wagner Farid Gattaz
Support Opportunities: Research Projects - Thematic Grants
FAPESP's process: 08/09861-0 - Effects of chronic inhibition of phospholipase A2 on membrane fluidity and cleavage of amyloid precursor protein in the prefrontal cortex and dorsal hippocampus of rats
Grantee:Heni Debs Skaf
Support Opportunities: Scholarships in Brazil - Scientific Initiation
FAPESP's process: 08/09494-8 - Effects of chronic inhibition of Phospholipase A2 on membrane fluidity and cleavage of amyloid precursor protein in the prefrontal cortex and dorsal hippocampus of rats
Grantee:Emanuelle Roberta da Silva
Support Opportunities: Scholarships in Brazil - Scientific Initiation