Dataset Information

Multiomics of synaptic junctions reveals altered lipid metabolism and signaling following environmental enrichment

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.

INSTRUMENT(S): Direct infusion MS - positive, Direct infusion MS - negative

SUBMITTER: Canan Has Nils Hoffmann

PROVIDER: MTBLS1531 | MetaboLights | 2021-09-27

REPOSITORIES: MetaboLights

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Dataset's files

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			Action	DRS
	MTBLS1531	Other
	FILES	Other
	a_MTBLS1531_DI-MS_negative__metabolite_profiling-1.txt	Txt
	a_MTBLS1531_DI-MS_negative__metabolite_profiling.txt	Txt
	a_MTBLS1531_DI-MS_positive__metabolite_profiling-1.txt	Txt

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Publications

Multiomics of synaptic junctions reveals altered lipid metabolism and signaling following environmental enrichment.

Borgmeyer Maximilian M Coman Cristina C Has Canan C Schött Hans-Frieder HF Li Tingting T Westhoff Philipp P Cheung Yam F H YFH Hoffmann Nils N Yuanxiang PingAn P Behnisch Thomas T Gomes Guilherme M GM Dumenieu Mael M Schweizer Michaela M Chocholoušková Michaela M Holčapek Michal M Mikhaylova Marina M Kreutz Michael R MR Ahrends Robert R

Cell reports 20211001 1

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 proo ...[more]

PMID: 34610315

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Project description:Environmental enrichment (EE) conditions have profound beneficial effects for reinstating cognitive ability in neuropathological disorders like Alzheimerâs disease (AD). While EE benefits involve epigenetic gene control mechanisms that comprise histone acetylation, the histone acetyltransferases (HATs) involved remain largely unknown. Here, we examine a role for Tip60 HAT action in mediating activity- dependent beneficial neuroadaptations to EE using the Drosophila CNS mushroom body (MB) as a well-characterized cognition model. We show that flies raised under EE conditions display enhanced MB axonal outgrowth, synapse protein production, histone acetylation induction and transcriptional activation of cognition linked genes when compared to their genotypically identical siblings raised under isolated conditions. Further, these beneficial changes are impaired in both Tip60 HAT mutant flies and APP neurodegenerative flies. While EE conditions provide only slight beneficial neuroadaptive changes in the APP neurodegenerative fly MB, such positive changes are significantly enhanced by increasing MB Tip60 HAT levels. Our results implicate Tip60 as a critical mediator of EE-induced benefits, and provide insight into synergistic behavioral and epigenetic based approaches for treatment of cognitive disorders. EE has been shown to positively impact gene expression profiles in the mouse brain that are enriched in functions such as neuronal structure, synaptic plasticity and neurotransmission. Thus, we asked whether the EE induced beneficial MB structural and synaptic changes we observe are accompanied by neuroadaptive transcriptional benefits in the Drosophila MB, and if so, is Tip60 HAT action required for this process. To address this question, we accessed EE induced beneficial transcriptional changes using microarray. We crossed our UAS-mCD8-GFP;Tip60E431Q flies or control UAS-mCD8-GFP flies to MB GAL4 OK-107 to simultaneously induce Tip60 HAT loss in the MB while tagging MB cells with GFP. Adult progeny were exposed to EE or ISO conditions. After conditioning, the GFP tagged MB Kenyon neurons were FACs purified from conditioned fly brains from each genotype to enrich for detection of an EE induced MB transcriptional response. RNA was isolated from the purified Kenyon MB neurons and transcriptional changes for each genotype were assessed using microarray analysis