TY  - JOUR
AU  - Borgmeyer, Maximilian
AU  - Coman, Cristina
AU  - Has, Canan
AU  - Schött, Hans-Frieder
AU  - Li, Tingting
AU  - Westhoff, Philipp
AU  - Cheung, Yam F H
AU  - Hoffmann, Nils
AU  - Yuanxiang, PingAn
AU  - Behnisch, Thomas
AU  - Gomes, Guilherme M
AU  - Dumenieu, Mael
AU  - Schweizer, Michaela
AU  - Chocholoušková, Michaela
AU  - Holčapek, Michal
AU  - Mikhaylova, Marina
AU  - Kreutz, Michael R
AU  - Ahrends, Robert
TI  - Multiomics of synaptic junctions reveals altered lipid metabolism and signaling following environmental enrichment.
JO  - Cell reports
VL  - 37
IS  - 1
SN  - 2211-1247
CY  - [New York, NY]
PB  - Elsevier
M1  - DZNE-2021-01561
SP  - 109797
PY  - 2021
N1  - CC BY-NC-ND
AB  - 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.
KW  - Amidohydrolases: metabolism
KW  - Animals
KW  - Chromatography, High Pressure Liquid
KW  - Endocannabinoids: metabolism
KW  - Hippocampus: cytology
KW  - Hippocampus: metabolism
KW  - Lipid Metabolism: genetics
KW  - Lipids: analysis
KW  - Male
KW  - Mice
KW  - Mice, Inbred C57BL
KW  - Monoacylglycerol Lipases: metabolism
KW  - Proteome: analysis
KW  - Proteomics: methods
KW  - Rats
KW  - Rats, Wistar
KW  - Receptors, AMPA: metabolism
KW  - Signal Transduction: genetics
KW  - Synapses: metabolism
KW  - Tandem Mass Spectrometry
KW  - Lipidomics (Other)
KW  - endocannabinoid signaling (Other)
KW  - enriched environment (Other)
KW  - multiomics (Other)
KW  - synaptic junctions (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:34610315
DO  - DOI:10.1016/j.celrep.2021.109797
UR  - https://pub.dzne.de/record/162906
ER  -