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      Dissecting the role of plasmalogen lipids in synapse function

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            Abstract

            Intro/Aims:

            This research aims to reveal fundamental mechanisms of neurodegenerative disorders by studying the consequences of disrupted lipid homeostasis in neurons by means of functional synapse assays and protein expression analyses. In neurodegeneration, the physiology of synapses is altered. Here, plasmalogen lipids are abundant and their peculiar conical shape makes them ideal in supporting vesicle fusion. In addition, plasmalogen levels decrease with pathological progression in Alzheimer’s disease. Since current evidence is correlative, we aim to provide tools to directly test whether plasmalogens support synaptic transmission for normal neuronal cell function. Specifically, we seek to prove that plasmalogens are required for synapse function and later explore their potential for neuro-regenerative supplementation therapies.

            Methods:

            My work will include western blot and ICC/IF detection of markers of mature neurons (NeuN, b3-tubulin) alongside established synaptic and vesicular markers (Synaptophysin1, PSD95, SV2, VAChT), and an assay for neurotransmitter release (Ach). Wet-lab assays will be performed on otherwise untreated differentiated cells alongside differentiated cells genetically silenced by using siRNA for plasmalogen biosynthetic enzymes FAR1 and PEDS1. Specifically, we will modulate plasmalogen levels in differentiated human SH-SY5Y cells as they embody a convenient model for developing assays. This work will be complemented with lipidomic analyses and will be soon translated to relevant iPSC-derived neurons.

            Statistics:

            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 (n=6) at one timepoint (e.g., normal vs plasmalogen-deficient) will use one-way ANOVA with Bonferroni correction (GraphPad Software).

            Content

            Author and article information

            Journal
            ScienceOpen Posters
            ScienceOpen
            16 April 2023
            Affiliations
            [1 ] Swansea University Medical School;
            Author notes
            Author information
            https://orcid.org/0009-0006-3109-1576
            https://orcid.org/0000-0001-5136-5921
            Article
            10.14293/P2199-8442.1.SOP-.PJDZ5Y.v1
            3e2e1c57-6ef4-49ca-84b2-bdc7d3b9ae74

            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
            : 16 April 2023
            Categories

            The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.
            Biochemistry,Neurology
            Plasmalogen,SH-SY5Y,synapse assembly,Alzheimer's disease

            References

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