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Originally published In Press as doi:10.1194/jlr.M500415-JLR200 on December 13, 2005

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Journal of Lipid Research, Vol. 47, 571-581, March 2006
Copyright © 2006 by American Society for Biochemistry and Molecular Biology

Docosahexaenoic acid facilitates cell maturation and ß-adrenergic transmission in astrocytes

Anindita Joardar*, Asish K. Sen{dagger} and Sumantra Das1,*

* Neurobiology Division, Indian Institute of Chemical Biology, Jadavpur, Kolkata 700032, India
{dagger} Carbohydrate Chemistry Division, Indian Institute of Chemical Biology, Jadavpur, Kolkata 700032, India

Published, JLR Papers in Press, December 13, 2005.

1 To whom correspondence should be addressed. e-mail: sdas{at}iicb.res.in

The effects of docosahexaenoic acid (DHA; 22:6 n-3), a major {omega}-3 PUFA in the mammalian brain, on the structure and function of astrocytes were studied using primary cultures from rat cerebra. Gas-liquid chromatography of methyl esters of FAs isolated from cultures exposed to individual FAs, namely, stearic acid, linoleic acid, arachidonic acid, and DHA, showed alterations in the lipid profiles of the membranes, with a preferential incorporation ofthe FA to which the cells were exposed. Immunofluorescence studies demonstrated that unlike treatment with other FAs, after which the astrocytes remained as immature radial forms, DHA-treated astrocytes showed distinct differentiation, having morphology comparable to those grown in normal serum-containing medium. Receptor binding studies to determine the concentration of various neurotransmitter receptors showed that DHA selectively increased the number of ß-adrenergic receptors (ß-ARs) compared with FA-untreated controls, suggesting a greater role of DHA on ß-AR expression in membranes. This was also reflected by an increase in downstream events of the ß-AR pathways, such as the induction of protein kinase A and glycogen turnover by isoproterenol (ISP), a ß-AR agonist in DHA-treated cells. Moreover, ISP completely transformed DHA-treated cells into mature astrocytes bearing long processes, as in cells grown under normal conditions. Together, our observations suggest that DHA plays a unique role in facilitating some of the vital functions of astrocytes in the developing brain.

Abbreviations: AA, arachidonic acid; ß-AR, ß-adrenergic receptor; DHA, docosahexaenoic acid; GFAP, glial fibrillary acidic protein; ISP, isoproterenol; LA, linoleic acid; LDH, lactate dehydrogenase; MTT, 3-[4,5-dimethylthiazol-2-yl]2,5-diphenyl-tetrazolium bromide; NMDA, N-methyl-D-aspartate; PIN, pindolol; PKA, protein kinase A; SA, stearic acid

Supplementary key words ß-adrenergic receptor • morphology • glycogen


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