Summary of Study ST003052

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR001901. The data can be accessed directly via it's Project DOI: 10.21228/M80H83 This work is supported by NIH grant, U2C- DK119886.

See: https://www.metabolomicsworkbench.org/about/howtocite.php

This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.

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Study IDST003052
Study TitleSynaptic vesicle lipidomics captures signatures of aging and synucleinopathy
Study SummaryUntargeted synaptic vesicle lipidomics analysis: Synaptic vesicles were isolated from six animals each of 1-month, 3-month, and 10-month old wild-type mice (JAX strain #: 000664), α-synuclein knockout mice (JAX strain #: 023837), and α-synuclein BAC mice (JAX strain #: 023837) using subcellular fractionation. Vesicles were concentrated using 3 kDa cutoff Amicon ultra centrifugal devices (Millipore). Pellets were resuspended in 100 µl water and homogenized. Protein concentration was determined using absorption at 280 nm. Samples were adjusted to the same concentration to a final volume of 200 µl in 50% methanol. All samples were mixed with a panel of 15 lipid internal standards (Splash LipidMix lot#330707), followed by lipid extraction as previously reported.1 Lipids were analyzed by LC-MS/MS on an Accucore C30 column (2.1 mm id x 150mm) under both positive and negative ion modes. Raw data files were searched and processed using LipidSearch 5.1 (Thermo Scientific) and normalized against the known amount of internal standard lipids for each sample, allowing for reliably quantitative measurements of all 15 categories of lipids.1 1 Bhawal, R., Fu, Q., Anderson, E.T., Gibson, G.E., and Zhang, S. (2021). Serum Metabolomic and Lipidomic Profiling Reveals Novel Biomarkers of Efficacy for Benfotiamine in Alzheimer's Disease. Int J Mol Sci 22.
Institute
Weill Cornell Medicine
DepartmentBrain and Mind Research Institute
LaboratoryBurré lab
Last NameBurré
First NameJacqueline
Address413 East 69th Street, BB-1024, New York, NY, 10021, USA
Emailjab2058@med.cornell.edu
Phone6469626155
Submit Date2024-01-19
Num Groups3
Total Subjects54
Raw Data AvailableYes
Raw Data File Type(s)raw(Thermo)
Analysis Type DetailLC-MS
Release Date2025-04-10
Release Version1
Jacqueline Burré Jacqueline Burré
https://dx.doi.org/10.21228/M80H83
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

Select appropriate tab below to view additional metadata details:

Project:

Project ID:PR001901
Project DOI:doi: 10.21228/M80H83
Project Title:Synaptic vesicle lipidomics captures signatures of aging and synucleinopathy
Project Type:MS quantitative analysis
Project Summary:Neurotransmitter release occurs through exocytosis of synaptic vesicles. α-Synuclein’s function and dysfunction in Parkinson’s disease and other synucleinopathies is tightly linked to synaptic vesicle binding. Age is the biggest risk factor for synucleinopathy, yet, age- and disease-induced changes in synaptic vesicles remain unexplored. Systematic analysis of the synaptic vesicle lipidome revealed specific changes in two mouse models of synucleinopathy over age. Strikingly, changes in mice lacking α-synuclein were more pronounced than changes in a humanized α-synucleinopathy mouse model, suggesting that loss of α-synuclein function is a major contributor to synaptic dysfunction. These findings not only provide new insights into synaptic vesicle biology and mechanisms of synucleinopathy, but also offer a baseline for further mechanistic exploration of age- and disease-related alterations in synaptic vesicles.
Institute:Weill Cornell Medicine
Department:Brain and Mind Research Institute
Laboratory:Burré lab
Last Name:Burré
First Name:Jacqueline
Address:413 East 69th Street, BB-1024, New York, NY, 10021, USA
Email:jab2058@med.cornell.edu
Phone:6469626155

Subject:

Subject ID:SU003167
Subject Type:Mammal
Subject Species:Mus musculus
Taxonomy ID:10090
Species Group:Mammals

Factors:

Subject type: Mammal; Subject species: Mus musculus (Factor headings shown in green)

mb_sample_id local_sample_id Genotype Age
SA331473SKB10mo pos1alpha-synuclein BAC 10 months
SA331474SKB10mo neg5alpha-synuclein BAC 10 months
SA331475SKB10mo pos2alpha-synuclein BAC 10 months
SA331476SKB10mo pos6alpha-synuclein BAC 10 months
SA331477SKB10mo pos4alpha-synuclein BAC 10 months
SA331478SKB10mo pos5alpha-synuclein BAC 10 months
SA331479SKB10mo pos3alpha-synuclein BAC 10 months
SA331480SKB10mo neg1alpha-synuclein BAC 10 months
SA331481SKB10mo neg1realpha-synuclein BAC 10 months
SA331482SKB10mo neg6alpha-synuclein BAC 10 months
SA331483SKB10mo neg3alpha-synuclein BAC 10 months
SA331484SKB10mo neg4alpha-synuclein BAC 10 months
SA331485SKB10mo neg2alpha-synuclein BAC 10 months
SA331461SKB1mo neg4alpha-synuclein BAC 1 month
SA331462SKB1mo neg5alpha-synuclein BAC 1 month
SA331463SKB1mo neg3alpha-synuclein BAC 1 month
SA331464SKB1mo pos6alpha-synuclein BAC 1 month
SA331465SKB1mo pos5alpha-synuclein BAC 1 month
SA331466SKB1mo pos4alpha-synuclein BAC 1 month
SA331467SKB1mo neg6alpha-synuclein BAC 1 month
SA331468SKB1mo pos3alpha-synuclein BAC 1 month
SA331469SKB1mo pos2alpha-synuclein BAC 1 month
SA331470SKB1mo neg1alpha-synuclein BAC 1 month
SA331471SKB1mo neg2alpha-synuclein BAC 1 month
SA331472SKB1mo pos1alpha-synuclein BAC 1 month
SA331486SKB3mo neg5alpha-synuclein BAC 3 months
SA331487SKB3mo neg6alpha-synuclein BAC 3 months
SA331488SKB3mo neg4alpha-synuclein BAC 3 months
SA331489SKB3mo neg2alpha-synuclein BAC 3 months
SA331490SKB3mo pos4alpha-synuclein BAC 3 months
SA331491SKB3mo pos5alpha-synuclein BAC 3 months
SA331492SKB3mo pos6alpha-synuclein BAC 3 months
SA331493SKB3mo pos3alpha-synuclein BAC 3 months
SA331494SKB3mo pos2alpha-synuclein BAC 3 months
SA331495SKB3mo neg1alpha-synuclein BAC 3 months
SA331496SKB3mo pos1alpha-synuclein BAC 3 months
SA331497SKB3mo neg3alpha-synuclein BAC 3 months
SA331510aKO10mo neg2alpha-synuclein knockout 10 months
SA331511aKO10mo neg1alpha-synuclein knockout 10 months
SA331512aKO10mo neg3alpha-synuclein knockout 10 months
SA331513aKO10mo pos6alpha-synuclein knockout 10 months
SA331514aKO10mo pos4alpha-synuclein knockout 10 months
SA331515aKO10mo neg4alpha-synuclein knockout 10 months
SA331516aKO10mo pos2alpha-synuclein knockout 10 months
SA331517aKO10mo pos1alpha-synuclein knockout 10 months
SA331518aKO10mo pos5alpha-synuclein knockout 10 months
SA331519aKO10mo pos3alpha-synuclein knockout 10 months
SA331520aKO10mo neg6alpha-synuclein knockout 10 months
SA331521aKO10mo neg5alpha-synuclein knockout 10 months
SA331498aKO1mo neg3alpha-synuclein knockout 1 month
SA331499aKO1mo pos3alpha-synuclein knockout 1 month
SA331500aKO1mo pos4alpha-synuclein knockout 1 month
SA331501aKO1mo pos2alpha-synuclein knockout 1 month
SA331502aKO1mo pos1alpha-synuclein knockout 1 month
SA331503aKO1mo neg1alpha-synuclein knockout 1 month
SA331504aKO1mo neg6alpha-synuclein knockout 1 month
SA331505aKO1mo pos5alpha-synuclein knockout 1 month
SA331506aKO1mo neg5alpha-synuclein knockout 1 month
SA331507aKO1mo pos6alpha-synuclein knockout 1 month
SA331508aKO1mo neg4alpha-synuclein knockout 1 month
SA331509aKO1mo neg2alpha-synuclein knockout 1 month
SA331522aKO3mo pos5alpha-synuclein knockout 3 months
SA331523aKO3mo pos4alpha-synuclein knockout 3 months
SA331524aKO3mo pos3alpha-synuclein knockout 3 months
SA331525aKO3mo pos1alpha-synuclein knockout 3 months
SA331526aKO3mo pos2alpha-synuclein knockout 3 months
SA331527aKO3mo neg1alpha-synuclein knockout 3 months
SA331528aKO3mo pos6alpha-synuclein knockout 3 months
SA331529aKO3mo neg4alpha-synuclein knockout 3 months
SA331530aKO3mo neg5alpha-synuclein knockout 3 months
SA331531aKO3mo neg6alpha-synuclein knockout 3 months
SA331532aKO3mo neg3alpha-synuclein knockout 3 months
SA331533aKO3mo neg2alpha-synuclein knockout 3 months
SA331412Blank neg1NA NA
SA331413Std neg1NA NA
SA331414Std pos3NA NA
SA331415Blank neg2NA NA
SA331416Std pos2NA NA
SA331417Blank pos1NA NA
SA331418Std neg2NA NA
SA331419Std neg3NA NA
SA331420Std neg4NA NA
SA331421Std pos4NA NA
SA331422Blank pos2NA NA
SA331423Std pos1NA NA
SA331436WT10mo pos5Wild-type 10 months
SA331437WT10mo pos6Wild-type 10 months
SA331438WT10mo pos4Wild-type 10 months
SA331439WT10mo neg3Wild-type 10 months
SA331440WT10mo pos2Wild-type 10 months
SA331441WT10mo pos1Wild-type 10 months
SA331442WT10mo pos3Wild-type 10 months
SA331443WT10mo neg5Wild-type 10 months
SA331444WT10mo neg2Wild-type 10 months
SA331445WT10mo neg4Wild-type 10 months
SA331446WT10mo neg1Wild-type 10 months
SA331447WT10mo neg6Wild-type 10 months
SA331424WT1mo neg4Wild-type 1 month
SA331425WT1mo neg5Wild-type 1 month
SA331426WT1mo neg1Wild-type 1 month
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Collection:

Collection ID:CO003160
Collection Summary:Synaptic vesicle were isolated by subcellular fractionation and concentrated
Sample Type:Brain

Treatment:

Treatment ID:TR003176
Treatment Summary:No treatments

Sample Preparation:

Sampleprep ID:SP003173
Sampleprep Summary:Synaptic vesicles were isolated from six animals each of 1-month, 3-month, and 10-month old wild-type mice (JAX strain #: 000664), α-synuclein knockout mice (JAX strain #: 023837), and α-synuclein BAC mice (JAX strain #: 023837) using subcellular fractionation. Vesicles were concentrated using 3 kDa cutoff Amicon ultra centrifugal devices (Millipore). Pellets were resuspended in 100 µl water and homogenized. Protein concentration was determined using absorption at 280 nm. Samples were adjusted to the same concentration to a final volume of 200 µl in 50% methanol. All samples were mixed with a panel of 15 lipid internal standards (Splash LipidMix lot#330707), followed by lipid extraction as previously reported (*1). Lipids were analyzed by LC-MS/MS on an Accucore C30 column (2.1 mm id x 150mm) under both positive and negative ion modes. Raw data files were searched and processed using LipidSearch 5.1 (Thermo Scientific) and normalized against the known amount of internal standard lipids for each sample, allowing for reliably quantitative measurements of all 15 categories of lipids (*1). References: 1. Bhawal, R., Fu, Q., Anderson, E.T., Gibson, G.E., and Zhang, S. (2021). Serum Metabolomic and Lipidomic Profiling Reveals Novel Biomarkers of Efficacy for Benfotiamine in Alzheimer's Disease. Int J Mol Sci 22.

Combined analysis:

Analysis ID AN005004 AN005005
Analysis type MS MS
Chromatography type Reversed phase Reversed phase
Chromatography system Thermo Vanquish Thermo Vanquish
Column Thermo Accucore C30 (150 x 2.1mm,2.6um) Thermo Accucore C30 (150 x 2.1mm,2.6um)
MS Type ESI ESI
MS instrument type Orbitrap Orbitrap
MS instrument name Thermo Q Exactive HF hybrid Orbitrap Thermo Q Exactive HF hybrid Orbitrap
Ion Mode POSITIVE NEGATIVE
Units area area

Chromatography:

Chromatography ID:CH003781
Instrument Name:Thermo Vanquish
Column Name:Thermo Accucore C30 (150 x 2.1mm,2.6um)
Column Temperature:55
Flow Gradient:0-4 min: 32% B; 4-5 min: 45% B; 5-8 min: 52% B; 8-11 min: 66% B; 11-14 min: 66% B; 14-18 min: 70% B, 18-21 min: 75% B; 21-25.01 min, 97% B; 25.01-30 min: 32% B
Flow Rate:0.26 ml/min
Solvent A:60% ACN, 40% H2O, 10 mM ammonium formate with 0.1% formic acid
Solvent B:90% IPA, 10% ACN, 10 mM ammonium formate with 0.1% formic acid
Chromatography Type:Reversed phase

MS:

MS ID:MS004744
Analysis ID:AN005004
Instrument Name:Thermo Q Exactive HF hybrid Orbitrap
Instrument Type:Orbitrap
MS Type:ESI
MS Comments:ESI voltage: 4kV Sheath gas flow rate: 50 (AU) Aux gas flow rate: 5 Sweep gas flow rate: 1 capillary temperature: 320°C S-Lens RF level: 60 Aux gas heater temperature: 350°C
Ion Mode:POSITIVE
  
MS ID:MS004745
Analysis ID:AN005005
Instrument Name:Thermo Q Exactive HF hybrid Orbitrap
Instrument Type:Orbitrap
MS Type:ESI
MS Comments:ESI voltage: 4kV Sheath gas flow rate: 50 (AU) Aux gas flow rate: 5 Sweep gas flow rate: 1 capillary temperature: 320°C S-Lens RF level: 60 Aux gas heater temperature: 350°C
Ion Mode:NEGATIVE
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