Inhibition of phospholipase A2 in rat brain modifies different membrane fluidity parameters in opposite ways

• Published in: Progress in neuro-psychopharmacology & biological psychiatry 2011-08, Vol.35 (7), p.1612-1617
• Main Authors: Schaeffer, Evelin L., Skaf, Heni D., Novaes, Barbara de A., da Silva, Emanuelle R., Martins, Beatriz A., Joaquim, Henrique D.G., Gattaz, Wagner F.
• Format: Article
• Language: English
• Subjects: Adult and adolescent clinical studies; Alzheimer disease; Alzheimer Disease - metabolism; Animals; Arachidonic acid; Arachidonic Acids - pharmacology; Biological and medical sciences; Brain - metabolism; Brain - physiology; Brain - physiopathology; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Drug Evaluation, Preclinical; Enzyme Inhibitors - pharmacology; Humans; Male; Medical sciences; Membrane fluidity; Membrane Fluidity - drug effects; Membrane Fluidity - physiology; Neurology; Neuropharmacology; Organic mental disorders. Neuropsychology; Organophosphonates - pharmacology; Pharmacology. Drug treatments; Phospholipase A2; Phospholipase A2 Inhibitors; Phospholipases A2 - blood; Phospholipases A2 - metabolism; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Rat; Rats; Rats, Wistar
• ISSN: 0278-5846; 1878-4216
• DOI: 10.1016/j.pnpbp.2011.05.001

Fluidity is an important neuronal membrane property and it is influenced by the concentration of polyunsaturated fatty acids (PUFAs) in membrane phospholipids. Phospholipase A2 (PLA2) is a key enzyme in membrane phospholipid metabolism, generating free PUFAs. In Alzheimer disease (AD), reduced PLA2 activity, specifically of calcium-dependent cytosolic PLA2 (cPLA2) and calcium-independent intracellular PLA2 (iPLA2), and phospholipid metabolism was reported in the frontal cortex and hippocampus. This study investigated the effects of in vivo infusion of the dual cPLA2 and iPLA2 inhibitor MAFP into rat brain on PLA2 activity and membrane fluidity parameters in the postmortem frontal cortex and dorsal hippocampus. PLA2 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 PLA2 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 cPLA2 and iPLA2 activities in AD brain might contribute to the cognitive impairment, in part, through alterations in membrane fluidity parameters. ► Inhibition of brain PLA2 alters different membrane fluidity parameters in opposite ways. ► Brain PLA2 inhibition reduces the flexibility of fatty acyl tails in the hydrophobic core. ► Brain PLA2 inhibition increases the fluidity in the region of lipid–water interface. ► Brain PLA2 inhibition increases the lateral diffusion of lipids in the hydrocarbon core. ► Membrane fluidity changes might contribute to cognitive and neuropathological alterations in AD.