Journal Article

DZNE-2021-01561

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Multiomics of synaptic junctions reveals altered lipid metabolism and signaling following environmental enrichment.

Borgmeyer, M. ; Coman, C. ; Has, C. ; Schött, H.-F. ; Li, T. ; Westhoff, P. ; Cheung, Y. F. H. ; Hoffmann, N. ; Yuanxiang, P. ; Behnisch, T. ; Gomes, G. M. ; Dumenieu, M. ; Schweizer, M. ; Chocholoušková, M. ; Holčapek, M. ; Mikhaylova, M. ; Kreutz, M. R.DZNE* ; Ahrends, R.

2021
Elsevier [New York, NY]

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Please use a persistent id in citations: doi:10.1016/j.celrep.2021.109797

Abstract: Membrane lipids and their metabolism have key functions in neurotransmission. Here we provide a quantitative lipid inventory of mouse and rat synaptic junctions. To this end, we developed a multiomics extraction and analysis workflow to probe the interplay of proteins and lipids in synaptic signal transduction from the same sample. Based on this workflow, we generate hypotheses about novel mechanisms underlying complex changes in synaptic connectivity elicited by environmental stimuli. As a proof of principle, this approach reveals that in mice exposed to an enriched environment, reduced endocannabinoid synthesis and signaling is linked to increased surface expression of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) in a subset of Cannabinoid-receptor 1 positive synapses. This mechanism regulates synaptic strength in an input-specific manner. Thus, we establish a compartment-specific multiomics workflow that is suitable to extract information from complex lipid and protein networks involved in synaptic function and plasticity.

Keyword(s): Amidohydrolases: metabolism (MeSH) ; Animals (MeSH) ; Chromatography, High Pressure Liquid (MeSH) ; Endocannabinoids: metabolism (MeSH) ; Hippocampus: cytology (MeSH) ; Hippocampus: metabolism (MeSH) ; Lipid Metabolism: genetics (MeSH) ; Lipids: analysis (MeSH) ; Male (MeSH) ; Mice (MeSH) ; Mice, Inbred C57BL (MeSH) ; Monoacylglycerol Lipases: metabolism (MeSH) ; Proteome: analysis (MeSH) ; Proteomics: methods (MeSH) ; Rats (MeSH) ; Rats, Wistar (MeSH) ; Receptors, AMPA: metabolism (MeSH) ; Signal Transduction: genetics (MeSH) ; Synapses: metabolism (MeSH) ; Tandem Mass Spectrometry (MeSH) ; Lipidomics ; endocannabinoid signaling ; enriched environment ; multiomics ; synaptic junctions

Note: CC BY-NC-ND

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Contributing Institute(s):

1. Clinical Neurophysiology and Memory (AG Düzel)

Research Program(s):

1. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)

Appears in the scientific report 2021

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Database coverage:
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