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

Anindita Joardar,Sumantra Das,Asish K. Sen

doi:10.1194/jlr.m500415-jlr200

Anindita Joardar, Sumantra Das + Show 1 more

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https://doi.org/10.1194/jlr.m500415-jlr200

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Abstract

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 of the 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 beta-adrenergic receptors (beta-ARs) compared with FA-untreated controls, suggesting a greater role of DHA on beta-AR expression in membranes. This was also reflected by an increase in downstream events of the beta-AR pathways, such as the induction of protein kinase A and glycogen turnover by isoproterenol (ISP), a beta-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.

Highlights

The effects of docosahexaenoic acid (DHA; 22:6 n-3), a major v-3 PUFA in the mammalian brain, on the structure and function of astrocytes were studied using primary cultures from rat cerebra
Of the various protocols using DHA conjugated to BSA, it was observed that treatment of cultured cells with 50 mM DHA conjugated to 15% or 50% BSA for 48 h followed by an additional incubation with fresh BSA conjugate for 24 h caused the maximum incorporation of DHA (6.3%), compared with 1.8% in untreated controls
This procedure of supplementation of DHA dissolved in 0.1% ethanol and 1% FBS was used for other FAs, namely, stearic acid (SA), linoleic acid (LA), and arachidonic acid (AA), and showed significant incorporation of the individual FA into the membranes of astrocytes

Summary

Introduction

The effects of docosahexaenoic acid (DHA; 22:6 n-3), a major v-3 PUFA in the mammalian brain, on the structure and function of astrocytes were studied using primary cultures from rat cerebra. Receptor binding studies to determine the concentration of various neurotransmitter receptors showed that DHA selectively increased the number of b-adrenergic receptors (b-ARs) compared with FA-untreated controls, suggesting a greater role of DHA on b-AR expression in membranes. This was reflected by an increase in downstream events of the b-AR pathways, such as the induction of protein kinase A and glycogen turnover by isoproterenol (ISP), a b-AR agonist in DHA-treated cells. The presence of such receptors suggests that astrocytes have the ability to integrate information in the brain in conjunction with neuronal processes. DHA is known to affect some of these neurotransmitter receptors in the brain [21,22,23,24], there is a dearth of information on its role in the neurotransmitter receptors of astrocytes

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