DHA enhances the noradrenaline release by SH-SY5Y cells.

Polyunsaturated fatty acids (PUFAs), particularly docosahexaenoic acid (DHA) and arachidonic acid (AA), are the main components of the phospholipids, in cerebral membranes. A dietary-induced cerebral DHA deficit results in altered behaviour and neurotransmission in rodents. To determine whether PUFA were acting on the neurotransmitter release machinery, we measured the release of [(3)H]-noradrenaline (NA) from SH-SY5Y neuroblastoma cells with modified PUFA membrane contents and from cells incubated with medium containing high DHA or AA. The membranes of cells incubated with 70 microM DHA for 3 days had 7.6-times more DHA in their ethanolamine glycerophospholipids, while the membranes of cells incubated with AA had 40% less. Incorporation of DHA enhanced basal [(3)H]-NA release (25%, p<0.05), but not KCl-evoked [(3)H]-NA release. Brief incubation with DHA during vesicle mobilization also strongly increased [3H]-NA release. AA had no effect. The genes encoding for the calcium sensor synaptotagmin 1, and for the two SNARE complex proteins syntaxin 1A and synaptobrevin 1 were not affected by PUFA incorporation, as indicated by assays for specific mRNAs and proteins. Thus both a high membrane DHA content and free DHA in the medium enhance the release of [(3)H]-NA from SH-SY5Y cells. This suggests that brain membrane DHA influences exocytosis, which then regulates neurotransmission.

Mathieu G ，Denis S ，Langelier B ，Denis I ，Lavialle M ，Vancassel S ... -  《-》

Docosahexaenoic acid (22:6n-3) enrichment of membrane phospholipids increases gap junction coupling capacity in cultured astrocytes.

Champeil-Potokar G ，Chaumontet C ，Guesnet P ，Lavialle M ，Denis I ... -  《EUROPEAN JOURNAL OF NEUROSCIENCE》

Inhibition of astroglial glutamate transport by polyunsaturated fatty acids: evidence for a signalling role of docosahexaenoic acid.

Grintal B ，Champeil-Potokar G ，Lavialle M ，Vancassel S ，Breton S ，Denis I ... -  《-》

Astrocytes in culture require docosahexaenoic acid to restore the n-3/n-6 polyunsaturated fatty acid balance in their membrane phospholipids.

Docosahexaenoic acid (DHA), the main n-3 polyunsaturated fatty acid (PUFA) in membranes, is particularly abundant in brain cells. Decreased cerebral concentrations of DHA, resulting from dietary n-3 deficiency, are associated with impaired cognitive function. Because the cellular causes of this impairment are still unknown, we need in vitro models that mimic the variations in n-3/n-6 PUFA seen in vivo. We have compared the PUFA profiles of hamster astrocytes cultured in medium supplemented with long-chain PUFA [DHA and/or arachidonic acid (AA)] with those of brain tissue from hamsters fed an n-6/n-3 PUFA-balanced diet or one lacking n-3 PUFA. Astrocytes were obtained from the brain cortex of newborn hamsters and cultured in minimum essential medium + 5% fetal calf serum (FCS) supplemented with DHA and/or AA for 10 days. The astrocytes cultured in medium + FCS had low n-3 PUFA contents, comparable to those of brain tissue from hamsters fed an n-3-deficient diet. We have shown that astrocytes grown in medium supplemented with DHA and/or AA, plus alpha-tocopherol to prevent lipid peroxidation, incorporated large amounts of these long-chain PUFA, so that the n-6/n-3 PUFA compositions of the phosphatidylethanolamine and phosphatidylcholine, the two main classes of membrane phospholipids, were greatly altered. Astrocytes cultured in medium plus DHA had a more physiological n-3 status, grew better, and retained their astrocyte phenotype. Thus astrocytes in culture are likely to be physiologically relevant only when provided with adequate DHA. This reliable method of altering membrane phospholipid composition promises to be useful for studying the influence of n-6/n-3 imbalance on astrocyte function.

Champeil-Potokar G ，Denis I ，Goustard-Langelier B ，Alessandri JM ，Guesnet P ，Lavialle M ... -  《JOURNAL OF NEUROSCIENCE RESEARCH》

Src family tyrosine kinases differentially modulate exocytosis from rat brain nerve terminals.

Baldwin ML ，Cammarota M ，Sim AT ，Rostas JA ... -  《-》