Polyunsaturated fatty acid biostatus, phospholipase A2 activity and brain white matter microstructure across adolescence

Abstract

Adolescence is a period of major brain white matter (WM) changes, and membrane lipid metabolism likely plays a critical role in brain WM myelination. Long-chain polyunsaturated fatty acids (LC-PUFAs) are essential components of cell membranes including oligodendrocytes, and LC-PUFA release and turnover in membranes is regulated by phospholipase A2 enzymes. To investigate the role of membrane lipid metabolism in healthy WM myelination across adolescence, the present study examined the relationship between membrane LC-PUFA biostatus, phospholipase A2 activity, and brain WM microstructure in healthy subjects aged 9–20 years (n = 30). Diffusion tensor imaging (DTI) was performed to measure average fractional anisotropy (FA) and diffusivity (indices sensitive to WM myelination) of nine major cerebral WM tracts. Blood samples were collected to measure erythrocyte membrane fatty acid concentrations and plasma intracellular phospholipase A2 activity (inPLA2). Plasma inPLA2 activity showed a significant U-curved association with WM radial diffusivity, and an inverted U-curved association with WM FA, independent of age. A significant positive linear correlation was observed between docosahexaenoic acid concentration and axial diffusivity in the corpus callosum. These findings suggest that there may be optimal physiological inPLA2 activity levels associated with healthy WM myelination in late childhood and adolescence. Myelination may be mediated by cleavage of docosahexaenoic acid from membrane phospholipids by inPLA2. These findings have implications for our understanding of the role of LC-PUFA homeostasis in myelin- related neurodevelopmental disorders.

Deficits in Docosahexaenoic Acid Accrual during Adolescence Reduce Rat Forebrain White Matter Microstructural Integrity: An in vivo Diffusion Tensor Imaging Study

“…Omega-3 (n-3) PUFAs including docosahexaenoic acid (DHA) and the omega-6 PUFA arachidonic acid (AA) have opposing effects on immuneinflammatory signaling, and metabolites of DHA have inflammation-resolving properties [16][17][18][19][20][21]. Importantly, emerging evidence suggests that PUFAs are associated with WMI in healthy subjects [22][23][24] and in patients with psychiatric disorders [25,26]. Meta-analyses indicate that schizophrenia [27], bipolar disorder [28], and unipolar depression [29] are associated with PUFA deficits including DHA.…”

N‐3 PUFA deficiency disrupts oligodendrocyte maturation and myelin integrity during brain development

“…While myelin impairment is a marker of most if not all neurodevelopmental disorders (Aoki et al, 2017; Kochunov et al, 2017), only little is known about the role of n‐3 PUFAs in the developmental myelination process. Some preclinical studies showed positive results with n‐3 LC‐PUFA supplementation on the maturation of oligodendrocytes and the expression of myelin related genes (Bernardo et al, 2017; Feltham et al, 2019; McNamara et al, 2017; Salvati et al, 2008; Siegert et al, 2017; Silva et al, 2017; Tian et al, 2011), yet others reported detrimental effects (Church et al, 2008; Church et al, 2009; Haubner et al, 2007). Moreover, clinical studies revealed a strong correlation between white matter integrity and n‐3 PUFA content in preterm infants, psychotic or aged subjects (Gu et al, 2016; Peters et al, 2009; Peters et al, 2013; Peters et al, 2014; Witte et al, 2014).…”

Lipides membranaires dans la schizophrénie et la psychose débutante : de potentiels biomarqueurs et pistes thérapeutiques ?

“…Enfin, une étude suggère d'une part que la myélinisation du cerveau à l'adolescence chez des sujets sains est corrélée négativement à l'activité de la phospholipase A2 intracellulaire et d'autre part que la concentration en DHA est corrélée positivement avec la myélinisation du corps calleux [43].…”