Inhibition of astroglial glutamate transport by polyunsaturated fatty acids: evidence for a signalling role of docosahexaenoic acid
Neurochemistry International. 2009-07-01; 54(8): 535-543
DOI: 10.1016/j.neuint.2009.02.018
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Grintal B(1), Champeil-Potokar G, Lavialle M, Vancassel S, Breton S, Denis I.
Author information:
(1)Unité de Nutrition et Régulation Lipidique des Fonctions Cérébrales – INRA –
78352 Jouy-en-Josas cedex, France.
Brain cells are especially rich in polyunsaturated fatty acids (PUFA), mainly
the n-3 PUFA docosahexaenoic acid (DHA) and the n-6 PUFA arachidonic acid (AA).
They are released from membranes by PLA2 during neurotransmission, and may
regulate glutamate uptake by astroglia, involved in controlling glutamatergic
transmission. AA has been shown to inhibit glutamate transport in several model
systems, but the contribution of DHA is less clear and has not been evaluated in
astrocytes. Because the high DHA content of brain membranes is essential for
brain function, we investigated the role of DHA in the regulation of astroglial
glutamate transport. We evaluated the actions of DHA and AA using cultured rat
astrocytes and suspensions of rat brain membranes (P1 fractions). DHA reduced
D-[(3)H]aspartate uptake by cultured astrocytes and cortical membrane
suspensions, while AA did not. This also occurred in astrocytes enriched with
alpha-tocopherol, indicating that it was not due to peroxidation products. The
reduction of d-[(3)H]aspartate uptake by DHA did not involve any change in the
concentrations of membrane-associated astroglial glutamate transporters (GLAST
and GLT-1), suggesting that DHA reduced the activity of the transporters. In
contrast with the inhibition induced by free-DHA, we found no effect of
membrane-bound DHA on D-[(3)H]aspartate uptake. Indeed, the uptake was similar
in astrocytes with varying amount of DHA in their membrane (induced by long-term
supplementation with DHA or AA). Therefore, DHA reduces glutamate uptake through
a signal-like effect but not through changes in the PUFA composition of the
astrocyte membranes. Also, reactive astrocytes, induced by a medium supplement
(G5), were insensitive to DHA. This suggests that DHA regulates synaptic
glutamate under basal condition but does not impair glutamate scavenging under
reactive conditions. These results indicate that DHA slows astroglial glutamate
transport via a specific signal-like effect, and may thus be a physiological
synaptic regulator.