Neuronal differentiation is triggered by oleic acid synthesized and released by astrocytes

Abstract

Unlike in the adult brain, the newborn brain speci®cally takes up serum albumin during the postnatal period, coinciding with the stage of maximal brain development. Here we report that albumin stimulates oleic acid synthesis by astrocytes from the main metabolic substrates available during brain development. Oleic acid released by astrocytes is used by neurons for the synthesis of phospholipids and is speci®cally incorporated into growth cones. Oleic acid promotes axonal growth, neuronal clustering, and expression of the axonal growth-associated protein-43, GAP-43; all these observations indicating neuronal differentiation. The effect of oleic acid on GAP-43 synthesis is brought about by the activation of protein kinase C, since it was prevented by inhibitors of this kinase, such as H-7, polymyxin or sphingosine. The expression of GAP-43 was signi®cantly increased in neurons co-cultured with astrocytes by the presence of albumin indicating that neuronal differentiation takes place in the presence of oleic acid synthesized and released by astrocytes in situ. In conclusion, during brain development the presence of albumin could play an important role by triggering the synthesis and release of oleic acid by astrocytes, which induces neuronal differentiation.

Oleic Acid and Cholinergic dysfunction in Down Syndrome Models of the Central Nervous System

“…Since previous studies have reported that oleic acid is preferentially incorporated into PC in the neuronal plasma membrane 8 : these findings are consistent with the significant reduction in monounsaturated fatty acid composition of phospholipids detected in the brains of people with Down's syndrome 33 . The incorporation of oleic acid to membrane phospholipids may alter the biophysical properties of the membrane and thereby regulate the activity of integral or peripheral membrane proteins 38 .…”

“…Membrane fluidity is critical for neurons and the incorporation of oleic acid-borne phospholipids into a discrete area of the membrane could substantially change membrane properties. In agreement with this: oleic acid is preferentially incorporated into neurite bases 8 : suggesting that increased fluidity is required at the sites of newly emerging axons and/or dendrites. This would facilitate the sprouting of the membrane during neurite growth together with enhanced flexibility for axon orientation 9 .…”

Signal transduction pathways involved in PPARβ/δ‐induced neuronal differentiation

“…OA has been shown to induce neuronal differentiation in rat cortical neurons (Tabernero et al, 2001). In the same cellular model and in the human neuroblastoma SH-SY5Y cells, a role for PPARb/d in neuronal differentiation has been proposed (Cimini et al, 2005;Di Loreto et al, 2007).…”

“…The treatment of SH-SY5Y cell line, established from a high malignant tumor with no N-myc amplification (Biedler et al, 1973), with phorbol esters leads to sympathetic neuronal differentiation with neurite outgrowth, increased synthesis of noradrenaline and expression of neuropeptide Y and growth-associated protein 43 (GAP-43) (Pahlman et al, 1981). In primary neuronal cultures oleic acid (OA) has been demonstrated to promote neuronal differentiation by PKC activation, leading to GAP-43 mRNA stabilization, neuronal clustering and neurite outgrowth (Tabernero et al, 2001). We have previously shown that some of OA-induced neuronal differentiation of SH-SY5Y cells is mediated by a class of transcriptional factors named peroxisome proliferator-activated receptors (PPARs), in particular the b isotype (Di Loreto et al, 2007).…”

Antioxidant effect of oleic acid and hydroxytyrosol in an experimental model similar to Huntington's disease

“…A la acción antioxidante del ácido oleico, que en neurodegeneración y patología neurológica solo ha sido demostrada en estudios experimentales, se le suma su demostrada acción neurotrófica, caracterizada por: i) un aumento en los niveles de expresión de las proteínas marcadoras de diferenciación neuronal GAP-43 y MAP-2; ii) crecimiento axonal; y iii) agrupación neuronal. Esta última, daría lugar a la presentación de estructuras similares a la materia gris, con agrupación de somas neuronales, y prolongación de sus axones hasta conectar con neuronas adyacentes (31,32).…”