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

Abstract

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. 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. The long-chain FA docosahexaenoic acid (DHA; 22:6n-3) constitutes a large proportion of membrane phospholipids in the central nervous system and is particularly concentrated in the aminophospholipids phosphatidylethanolamine and phosphatidylserine of membranes. DHA can also be synthesized from the shorter chain precursor a-linolenic acid (18:3n-3), an essential FA that cannot be synthesized de novo by animal tissues and must be obtained from the diet (1). The importance of DHA in maintaining the structural and functional integrity of membranes is highlighted by the fact that it cannot be easily depleted from the brain (2). It is now well recognized that DHA is essential for normal brain development in animals and humans (3). In the human brain, the major accumulation occurs during the last period of gestation (4). DHA deficiency causes impairment of learning and memory. Supplementation of DHA reverses the effect by increasing the number of Fos-positive neurons and promoting neurite outgrowth and the size of the cell body in the CA1 hippocampus (5, 6) and restores long-term potentiation in aged rats (7,8). DHA plays a crucial role in membrane order (membrane fluidity), the regulation of phosphatidylserine levels (9), and the protection of neural cells from apoptotic death (10-12). Changes in energy metabolism induced by n-3 deficiency could result from functional alteration in glucose transporters (13).Although much of our understanding of the effect of DHA on the central nervous system has involved studies of neurons, existing knowledge regarding its effect on astrocytes is scarce. Astroglial cells constitute the major cells of the adult mammalian brain, outnumbering neurons by manyfold. Like neurons, astrocytes also undergo morphogenesis both in vivo (14) and in vitro (15,16) characterized by changes in cell shape. In addition to maintaining the microenvironment of neurons, astrocytes play a constitutive role in the formation of the bloodbrain barrier (17), represent the major glycogen depots of brain (18), support immune defense by producing various immunoactive cytokines (17), and maintain the external potassium concentration (19). Additionally, astrocytes possess myriad neurotransmitter receptors (20), most of which are transmembrane in nature and...

Perinatal n-3 fatty acid deficiency selectively reduces myo-inositol levels in the adult rat PFC: an in vivo 1H-MRS study

“…Third, rat astrocyte ontogenesis occurs predominantly during prenatal development (28), and mI concentrations were reduced by perinatal, but not postweaning, ALAdeficiency (present results). Furthermore, DHA is required for the normal growth and maturation of cortical astrocytes in culture (29). Fourth, the astrocyte-specific glucose transporter (45 kDa GLUT1), but not the neuronalspecific glucose transporter (GLUT3), is significantly reduced in the cortex of DHA-deficient rats (30).…”

Effect of Fatty Acids Isolated from Edible Oils Like Mustard, Linseed or Coconut on Astrocytes Maturation

“…of ethanol, 0.15%). One percent FCS and 0.1 mM ascorbic acid (as antioxidant) were added and cells were cultured for a further period of 48 h (Joardar et al 2006). FAs from mustard, coconut, and linseed oils were supplemented in the astrocyte culture.…”

“…Primary cultures of glial cells from the cerebra of neonates (<24 h old) were prepared as described earlier (Joardar et al 2006). In short, cerebra were dissected aseptically, washed, and pooled in an isotonic balanced salt solution (BSS).…”

“…The mammalian brain is highly enriched in the polyunsaturated FA (PUFA), docosahexaenoic acid (DHA) (22:6n-3), which is essential for normal visual and cognitive development (Anderson et al 1990). Our recent studies have demonstrated the importance of DHA in astrocyte maturation (Joardar et al 2006).…”

Increased β2-Adrenergic Receptor Activity by Thyroid Hormone Possibly Leads to Differentiation and Maturation of Astrocytes in Culture

“…Specific b-AR binding in the astrocyte membranes were carried out using 2 nM [ 125 I]PIN in absence and presence of 100 lM propranolol (Sigma) as described earlier (Joardar et al 2006). (-)-Pindolol (Research Biochemicals International, Natick, MA, USA) was iodinated with Na 125 I (Bhaba Atomic Research Centre, Mumbai, India) to a specific activity of 2.2 Ci/lmol (Witkin and Harden 1981).…”