Lyso-Lipid-Induced Oligodendrocyte Maturation Underlies Restoration of Optic Nerve Function

Anddre Osmar Valdivia; Sanjoy K. Bhattacharya

doi:10.1523/ENEURO.0429-21.2022

Lyso-Lipid-Induced Oligodendrocyte Maturation Underlies Restoration of Optic Nerve Function

Anddre Osmar Valdivia, Sanjoy K. Bhattacharya

Research output: Contribution to journal › Article › peer-review

Abstract

Protein hyperdeimination 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 hyperdeimination and stimulation of oligodendrocyte maturation, while in vivo investigations recorded optic nerve function improvement following optic nerve injections of LPC 18:1, in contrast with 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.

Original language	English (US)
Article number	ENEURO.0429-21.2022
Journal	eNeuro
Volume	9
Issue number	1
DOIs	https://doi.org/10.1523/ENEURO.0429-21.2022
State	Published - Jan 1 2022
Externally published	Yes

Keywords

Deimination
LPC 18:1
Myelin
Oligodendrocytes
Optic nerve
Remyelination

ASJC Scopus subject areas

Neuroscience(all)

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10.1523/ENEURO.0429-21.2022

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title = "Lyso-Lipid-Induced Oligodendrocyte Maturation Underlies Restoration of Optic Nerve Function",

abstract = "Protein hyperdeimination 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 hyperdeimination and stimulation of oligodendrocyte maturation, while in vivo investigations recorded optic nerve function improvement following optic nerve injections of LPC 18:1, in contrast with 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.",

keywords = "Deimination, LPC 18:1, Myelin, Oligodendrocytes, Optic nerve, Remyelination",

author = "Valdivia, {Anddre Osmar} and Bhattacharya, {Sanjoy K.}",

note = "Funding Information: This work was supported by the US Department of Defense Grant WH-X81-160715; and Department of Health and Human Services | National Institutes of Health | National Eye Institute Grants EY-027257 and EY-14801; and an unrestricted grant to the University of Miami from Research to Prevent Blindness. Publisher Copyright: {\textcopyright} 2022 Valdivia and Bhattacharya.",

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N1 - Funding Information: This work was supported by the US Department of Defense Grant WH-X81-160715; and Department of Health and Human Services | National Institutes of Health | National Eye Institute Grants EY-027257 and EY-14801; and an unrestricted grant to the University of Miami from Research to Prevent Blindness. Publisher Copyright: © 2022 Valdivia and Bhattacharya.

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N2 - Protein hyperdeimination 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 hyperdeimination and stimulation of oligodendrocyte maturation, while in vivo investigations recorded optic nerve function improvement following optic nerve injections of LPC 18:1, in contrast with 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.

AB - Protein hyperdeimination 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 hyperdeimination and stimulation of oligodendrocyte maturation, while in vivo investigations recorded optic nerve function improvement following optic nerve injections of LPC 18:1, in contrast with 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.

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Lyso-Lipid-Induced Oligodendrocyte Maturation Underlies Restoration of Optic Nerve Function

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Keywords

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