Inhibition of phospholipase A(2) in rat brain modifies different membrane fluidity parameters in opposite ways

Author(s)

Schaeffer, Evelin L. ^[1] ; Skaf, Heni D. ^[2] ; Novaes, Barbara de A. ^[2] ; da Silva, Emanuelle R. ^[2] ; Martins, Beatriz A. ^[2] ; Joaquim, Henrique D. G. ^[2] ; Gattaz, Wagner F. ^[2]

Affiliation

^[1] Univ Sao Paulo, Fac Med, Lab Neurosci LIM 27, Dept Psychiat, BR-05403010 Sao Paulo - Brazil

^[2] Univ Sao Paulo, Fac Med, Lab Neurosci LIM 27, Inst Psychiat, BR-05403010 Sao Paulo - Brazil

• Document type: Review article
• Source: PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY; v. 35, n. 7, p. 1612-1617, AUG 15 2011.
• Web of Science Citations: 12

Abstract

Fluidity is an important neuronal membrane property and it is influenced by the concentration of polyunsaturated fatty acids (PUFAs) in membrane phospholipids. Phospholipase A(2) (PLA(2)) is a key enzyme in membrane phospholipid metabolism, generating free PUFAs. In Alzheimer disease (AD), reduced PLA(2) activity, specifically of calcium-dependent cytosolic PLA(2) (cPLA(2)) and calcium-independent intracellular PLA(2) (iPLA(2)), and phospholipid metabolism was reported in the frontal cortex and hippocampus. This study investigated the effects of in vivo infusion of the dual cPLA(2) and iPLA(2) inhibitor MAFP into rat brain on PLA(2) activity and membrane fluidity parameters in the postmortem frontal cortex and dorsal hippocampus. PLA(2) activity was measured by radioenzymatic assay and membrane fluidity was determined by fluorescence anisotropy technique using three different probes: DPH, TMA-DPH, and pyrene. MAFP significantly inhibited PLA(2) activity, reduced the flexibility of fatty acyl chains (indicated by increased DPH anisotropy), increased the fluidity in the lipid-water interface (indicated by decreased TMA-DPH anisotropy), and increased the lipid lateral diffusion in the hydrocarbon core (represented by pyrene excimer formation) of membranes in both brain areas. The findings suggest that reduced cPLA(2) and iPLA(2) activities in AD brain might contribute to the cognitive impairment, in part, through alterations in membrane fluidity parameters. (C) 2011 Elsevier Inc. All rights reserved. (AU)

• FAPESP's process: 05/52899-0 - 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: Beatriz Arakawa Martins
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 05/52898-4 - 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: Henrique Dametto Giroud Joaquim
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• 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