Polyunsaturated Fatty Acid Supplementation Stimulates Differentiation of Oligodendroglia Cells

Abstract

Dietary polyunsaturated fatty acids (PUFAs) have been postulated as alternative supportive treatment for multiple sclerosis, since they may promote myelin repair. We set out to study the effect of supplementation with n-3 and n-6 PUFAs on OLN-93 oligodendroglia and rat primary oligodendrocyte differentiation in vitro. It appeared that OLN-93 cells actively incorporate and metabolise the supplemented PUFAs in their cell membrane. The effect of PUFAs on OLN-93 differentiation was further assessed by morphological and Western blot evaluation of markers of oligodendroglia differentiation: 2′,3′-cyclic nucleotide 3′-phosphodiesterase (CNP), zonula occludens-1 (ZO-1) and myelin-associated glycoprotein (MAG). Supplementation of the OLN-93 cells with n-3 and n-6 PUFAs increased the degree of differentiation determined by morphological analysis. Moreover, CNP protein expression was significantly increased by γ-linolenic acid (GLA, 18:3n-6) supplementation. In accordance with the OLN-93 results, studies with rat primary oligodendrocytes, a more advanced model of cell differentiation, showed GLA supplementation to promote oligodendrocyte differentiation. Following GLA supplementation, increased numbers of proteolipid protein (PLP)-positive oligodendrocytes and increased myelin sheet formation was observed during differentiation of primary oligodendrocytes. Moreover, increased CNP, and enhanced PLP and myelin basic protein expression were found after GLA administration. These studies provide support for the dietary supplementation of specific PUFAs to support oligodendrocyte differentiation and function.

The challenge of understanding cerebral white matter injury in the premature infant

“…There is some evidence that undernutrition slows or blocks oligodendrocyte maturation, thereby resulting in hypomyelination (Robain and Ponsot, 1978) and others have observed a block in oligodendrocyte maturation in premature infants with white matter injury (Billiards et al, 2008, Buser et al, 2012). A role for polyunsaturated fatty acids has been suggested as supplementation with omega-3 or omega-6 fatty acids stimulates differentiation of oligodendrocytes in culture (van Meeteren et al, 2006). However, the direct or indirect effects of undernutrition on oligodendrocytes and myelination require more detailed investigation.…”

Morphological changes do not reflect biochemical and functional differentiation in OLN-93 oligodendroglial cells

“…in the study of apoptosis (Brand and Yavin, 2005;Burgmaier et al, 2000;Gerstner et al, 2005Gerstner et al, , 2006Kameshwar-Rao et al, 1999;Uberti et al, 1999), membrane trafficking (Gielen et al, 2006;Zhang et al, 2005), oxidative stress (Ernst et al, 2004;Stahnke et al, 2007), oligodendroglial proteins (Maier et al, 2006) and differentiation (Li et al, 2007;van Meeteren et al, 2006). Although used in the study of several aspects of oligodendroglial biology, an electrophysiological characterisation of OLN-93 oligodendroglial cells has never been performed.…”

High-resolution structural model of porcine P2 myelin membrane protein with associated fatty acid ligand: Fact or artifact?

“…In particular, the a type is associated with decreasing cardiovascular death; fatal heart arrhythmia (Breslow, 2006); and alterations of membrane fluidity, cellular responses, ion transport (Philbrick et al, 1987), and learning ability (Yamamoto et al, 2007). The expression of CNP was significantly increased by g-linolenic acid (18:3, n-6, n-9, n-12), as well as an increase in proteolipid-positive oligodendrocytes, with increased myelin sheet formation (Meeteren et al, 2006). This fatty acid also reduces body fat content (Takada et al, 1993).…”