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Inhibition of astroglial glutamate transport by polyunsaturated fatty acids: evidence for a signalling role of docosahexaenoic acid.
Neurochem Int. 2009 Jul; 54(8):535-43.NI

Abstract

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.

Authors+Show Affiliations

Unité de Nutrition et Régulation Lipidique des Fonctions Cérébrales - INRA - 78352 Jouy-en-Josas cedex, France.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

19428799

Citation

Grintal, Barbara, et al. "Inhibition of Astroglial Glutamate Transport By Polyunsaturated Fatty Acids: Evidence for a Signalling Role of Docosahexaenoic Acid." Neurochemistry International, vol. 54, no. 8, 2009, pp. 535-43.
Grintal B, Champeil-Potokar G, Lavialle M, et al. Inhibition of astroglial glutamate transport by polyunsaturated fatty acids: evidence for a signalling role of docosahexaenoic acid. Neurochem Int. 2009;54(8):535-43.
Grintal, B., Champeil-Potokar, G., Lavialle, M., Vancassel, S., Breton, S., & Denis, I. (2009). Inhibition of astroglial glutamate transport by polyunsaturated fatty acids: evidence for a signalling role of docosahexaenoic acid. Neurochemistry International, 54(8), 535-43. https://doi.org/10.1016/j.neuint.2009.02.018
Grintal B, et al. Inhibition of Astroglial Glutamate Transport By Polyunsaturated Fatty Acids: Evidence for a Signalling Role of Docosahexaenoic Acid. Neurochem Int. 2009;54(8):535-43. PubMed PMID: 19428799.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Inhibition of astroglial glutamate transport by polyunsaturated fatty acids: evidence for a signalling role of docosahexaenoic acid. AU - Grintal,Barbara, AU - Champeil-Potokar,Gaëlle, AU - Lavialle,Monique, AU - Vancassel,Sylvie, AU - Breton,Sylvie, AU - Denis,Isabelle, Y1 - 2009/03/05/ PY - 2008/12/04/received PY - 2009/02/23/accepted PY - 2009/5/12/entrez PY - 2009/5/12/pubmed PY - 2009/7/16/medline SP - 535 EP - 43 JF - Neurochemistry international JO - Neurochem. Int. VL - 54 IS - 8 N2 - 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. SN - 1872-9754 UR - https://www.unboundmedicine.com/medline/citation/19428799/Inhibition_of_astroglial_glutamate_transport_by_polyunsaturated_fatty_acids:_evidence_for_a_signalling_role_of_docosahexaenoic_acid_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0197-0186(09)00077-1 DB - PRIME DP - Unbound Medicine ER -