TY - JOUR T1 - Lyso-lipid induced oligodendrocytes maturation underlie restoration of optic nerve function JF - eneuro JO - eNeuro DO - 10.1523/ENEURO.0429-21.2022 SP - ENEURO.0429-21.2022 AU - Anddre Osmar Valdivia AU - Sanjoy K. Bhattacharya Y1 - 2022/01/13 UR - http://www.eneuro.org/content/early/2022/01/12/ENEURO.0429-21.2022.abstract N2 - Protein hyper-deimination and deficiency of lyso-phospholipids (LPC 18:1) has been associated with the pathology of demyelinating disease in both humans and mice. We uncovered interesting biology of LPC 18:1, in which LPC 18:1 induced optic nerve function restoration through oligodendrocyte maturation and remyelination in mouse model systems. Our in vitro studies show LPC 18:1 protection against neuron-ectopic hyper-deimination and stimulation of oligodendrocyte maturation, while in vivo investigations recorded optic nerve function improvement following optic nerve injections of LPC 18:1, in contrast to LPC 18:0. Thus just a change in a single bond renders a dramatic alternation in biological function. The incorporation of isobaric C13-histidine in newly synthesized myelin proteins and quantitative proteome shifts are consistent with remyelination underlying restoration in optic nerve function. These results suggest that exogenous LPC 18:1 may provide a therapeutic avenue for stemming vision loss in demyelinating diseases.Significance StatementDemyelinating diseases have been associated with an increase in aberrant hyper-deimination and deficiencies in neuronal lipids (LPC 18:1). We demonstrate that exogenous delivery of LPC 18:1 can prevent hyper-deimination and restore optic nerve function in demyelinating optic nerves. We show that this effect is mediated by induction of oligodendrocyte maturation and remyelination. These effects contrast the demyelinating effects of LPC 18:0, which only differs by a single bond, pointing towards a fundamental change in our understanding of lipid behavior. Our findings highlight the potential translational implications of LPC 18:1 in restoring optic nerve function in demyelinating diseases. ER -