- Record: found
- Abstract: found
- Poster: found
The Role of Plasmalogen Lipids in Synaptic Assembly and Function: Implications for Neurodegenerative Processes
Abstract
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.
My work includes western blot and ICC/IF detection of markers of mature neurons (NeuN, B3-tubulin) alongside established synaptic and vesicular markers (Synaptophysin1, PSD95, SV2, VAChT), as well as live cell vesicular stains. Wet-lab assays were performed on otherwise untreated differentiated cells alongside differentiated cells genetically silenced by using shRNA for plasmalogen biosynthetic enzyme FAR1. Specifically, I have modulated plasmalogen levels in differentiated human SH-SY5Y cells and ReNcell VM as they embody convenient models for developing assays and monitoring synapse assembly. This work will be complemented with lipidomic analyses and will be soon translated to relevant iPSC-derived neurons.
The data from lipidomic and synaptic assays were normally distributed. Comparison of multiple groups (n=18) at one timepoint (e.g., normal vs plasmalogen-deficient) used one-way ANOVA with Bonferroni correction (GraphPad Software).
Content
Author and article information
References
Shipley Mackenzie M., Mangold Colleen A., Szpara Moriah L.. Differentiation of the SH-SY5Y Human Neuroblastoma Cell Line. Journal of Visualized Experiments. (108)2016. MyJove Corporation. [Cross Ref]
Goodenowe Dayan B., Senanayake Vijitha. Relation of Serum Plasmalogens and APOE Genotype to Cognition and Dementia in Older Persons in a Cross-Sectional Study. Brain Sciences. Vol. 9(4)2019. MDPI AG. [Cross Ref]
Pamies David, Vujić Tatjana, Schvartz Domitille, Boccard Julien, Repond Cendrine, Nunes Carolina, Rudaz Serge, Sanchez Jean-Charles, González-Ruiz Víctor, Zurich Marie-Gabrielle. Digoxin Induces Human Astrocyte Reaction In Vitro. Molecular Neurobiology. Vol. 60(1):84–97. 2023. Springer Science and Business Media LLC. [Cross Ref]