Dissecting the role of plasmalogen lipids in synapse function and neurodegeneration by interdisciplinary lipidomics

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Dissecting the role of plasmalogen lipids in synapse function and neurodegeneration by interdisciplinary lipidomics

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Author(s): Iwan Gane ¹ ^, , Kathryn Sinclair ¹ , Ann Hunter ² , Roberto Angelini ¹

Publication date (Electronic preprint): 15 April 2023

Journal: ScienceOpen Posters

Publisher: ScienceOpen

Keywords: Synapse, Lipidomics, Plasmalogen, Neuroscience, Neurodegeneration

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Abstract

Introduction

More than 520,000 people in the UK suffer from dementia caused by Alzheimer’s Disease (AD), a number set to rise towards 1 million by 2025 with the resultant cost to the economy expected to surpass £25 billion. With currently no effective treatments for patients with AD or dementia, it is crucial that research advances our understanding of these conditions with an aim to bring therapies to the fore. Synaptic dysfunction develops early in neurodegeneration, driving the gradual impairment of memory, sensation, and cognition. This correlates with the loss of plasmalogen phospholipids, which are enriched at synapses where their conical geometry is believed to ease synaptic vesicle fusion. Direct assessment of the role of plasmalogens at synapses has yet to be carried out, which is our goal.

Methods

We have developed a neuronal model using the neuroblastoma cell line, SH-SY5Y, to study the effects of plasmalogen levels on synapse formation and function following post-transcriptional silencing of plasmalogen biosynthetic enzymes. We are developing a novel quantitative shotgun lipidomics approach for the study of plasmalogens in neuronal cells, and with this data in parallel with immunocytochemistry, Western-blot and neurotransmitter assays, we will determine and characterise the role of plasmalogens at synapses. Furthermore, we will assess the capacity of plasmalogen precursor supplementation to restore plasmalogen levels and hence to abrogate disruption of synapse formation and function, endeavouring to open a future treatment direction for AD.

Approach for Statistical Analysis

Based on our preliminary data and previous literature, we expect the data from lipidomic and synaptic assays to be normally distributed. Comparison of multiple groups at one time point (e.g., normal vs plasmalogen-deficient vs plasmalogen-supplemented groups) will use one-way ANOVA with Bonferroni correction (GraphPad Software). Estimating a 50% decrease of plasmalogen levels and/or synaptic puncta upon KD and a 50% increase upon supplementation, SD=20%, eq

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Author and article information

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Title: ScienceOpen Posters

Publisher: ScienceOpen

Publication date (Electronic preprint): 15 April 2023

Affiliations

[1 ] Institute of Life Sciences 1, Singleton Campus, Swansea University, SA2 8PP;

[2 ] NMSF, Swansea University Medical School, Singleton Park, Swansea SA2 8PP;

Author notes

[* ]Email: 831395@ 123456swansea.ac.uk .

Author information

Iwan Gane https://orcid.org/0009-0004-3758-2822

Article

DOI: 10.14293/P2199-8442.1.SOP-.PUAX3V.v1

SO-VID: 8cd76973-57b0-4bb1-9d28-afc740b0ce96

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This work has been published open access under Creative Commons Attribution License CC BY 4.0 , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Conditions, terms of use and publishing policy can be found at www.scienceopen.com .

History

Date received : 15 April 2023

Funding

Funded by: funder-id http://dx.doi.org/10.13039/501100000288, Royal Society;

References

Bozelli José Carlos, Azher Sayed, Epand Richard M.. Plasmalogens and Chronic Inflammatory Diseases. Frontiers in Physiology. Vol. 12:2021. Frontiers Media SA. [Cross Ref]
Braverman Nancy E., Moser Ann B.. Functions of plasmalogen lipids in health and disease. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease. Vol. 1822(9):1442–1452. 2012. Elsevier BV. [Cross Ref]
Murphy Robert C.. Free-Radical-Induced Oxidation of Arachidonoyl Plasmalogen Phospholipids: Antioxidant Mechanism and Precursor Pathway for Bioactive Eicosanoids. Chemical Research in Toxicology. Vol. 14(5):463–472. 2001. American Chemical Society (ACS). [Cross Ref]
Bozelli José Carlos, Epand Richard M.. Plasmalogen Replacement Therapy. Membranes. Vol. 11(11)2021. MDPI AG. [Cross Ref]
Dravid Anusha, Raos Brad, Svirskis Darren, O’Carroll Simon J.. Optimised techniques for high-throughput screening of differentiated SH-SY5Y cells and application for neurite outgrowth assays. Scientific Reports. Vol. 11(1)2021. Springer Science and Business Media LLC. [Cross Ref]
Wood Paul L. Lipidomics of Alzheimer's disease: current status. Alzheimer's Research & Therapy. Vol. 4(1)2012. Springer Science and Business Media LLC. [Cross Ref]
Zhou Yulong, Yu Ning, Zhao Jie, Xie Zhenming, Yang Zhaonan, Tian Bing. Advances in the Biosynthetic Pathways and Application Potential of Plasmalogens in Medicine. Frontiers in Cell and Developmental Biology. Vol. 8:2020. Frontiers Media SA. [Cross Ref]

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[1] Bozelli José Carlos, Azher Sayed, Epand Richard M.. Plasmalogens and Chronic Inflammatory Diseases. Frontiers in Physiology. Vol. 12:2021. Frontiers Media SA. [Cross Ref]

[2] Braverman Nancy E., Moser Ann B.. Functions of plasmalogen lipids in health and disease. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease. Vol. 1822(9):1442–1452. 2012. Elsevier BV. [Cross Ref]

[3] Murphy Robert C.. Free-Radical-Induced Oxidation of Arachidonoyl Plasmalogen Phospholipids: Antioxidant Mechanism and Precursor Pathway for Bioactive Eicosanoids. Chemical Research in Toxicology. Vol. 14(5):463–472. 2001. American Chemical Society (ACS). [Cross Ref]

[4] Bozelli José Carlos, Epand Richard M.. Plasmalogen Replacement Therapy. Membranes. Vol. 11(11)2021. MDPI AG. [Cross Ref]

[5] Dravid Anusha, Raos Brad, Svirskis Darren, O’Carroll Simon J.. Optimised techniques for high-throughput screening of differentiated SH-SY5Y cells and application for neurite outgrowth assays. Scientific Reports. Vol. 11(1)2021. Springer Science and Business Media LLC. [Cross Ref]

[6] Wood Paul L. Lipidomics of Alzheimer's disease: current status. Alzheimer's Research & Therapy. Vol. 4(1)2012. Springer Science and Business Media LLC. [Cross Ref]

[7] Zhou Yulong, Yu Ning, Zhao Jie, Xie Zhenming, Yang Zhaonan, Tian Bing. Advances in the Biosynthetic Pathways and Application Potential of Plasmalogens in Medicine. Frontiers in Cell and Developmental Biology. Vol. 8:2020. Frontiers Media SA. [Cross Ref]

Dissecting the role of plasmalogen lipids in synapse function and neurodegeneration by interdisciplinary lipidomics

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