Summary of Study ST003176

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 PR001975. The data can be accessed directly via it's Project DOI: 10.21228/M8F723 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 IDST003176
Study TitleChronic manganese exposure disrupts glutamatergic signaling and alters behavior in APP/PSEN1 mice.
Study Typeuntargeted metabolomics analysis
Study SummaryPathological changes in Alzheimer’s disease (AD) begin decades before cognitive symptoms appear. Chronic exposure to environmental neurotoxins like manganese (Mn) from sources such as air pollution and water can impact disease development across decades. Mn toxicity can lead to motor and neuropsychiatric symptoms resembling Parkinson's disease, attributed to its accumulation in globus pallidus. In contrast, the impact of chronic lower-level exposures on normal and neuropathological brain function is unknown. We tested whether 10 months of a high Mn diet (2400 ppm) could alter aspects of glutamate signaling in APP/PSEN1 mice to further exacerbate cognitive impairments compared to control fed animals (70 ppm). This study supports the potential role for chronic environmental exposures in the development of Alzheimer’s disease associated neuropathology.
Institute
Vanderbilt University
DepartmentChemistry
LaboratoryCenter for Innovative Technology
Last NameCODREANU
First NameSIMONA
Address1234 STEVENSON CENTER LANE
EmailSIMONA.CODREANU@VANDERBILT.EDU
Phone6158758422
Submit Date2024-04-18
Num Groups6
Total Subjects53
Num Males26
Num Females27
Study CommentsThis study supports the potential role for chronic environmental exposures in the development of Alzheimer’s disease associated neuropathology.
Raw Data AvailableYes
Raw Data File Type(s)raw(Thermo)
Analysis Type DetailLC-MS
Release Date2024-10-18
Release Version1
SIMONA CODREANU SIMONA CODREANU
https://dx.doi.org/10.21228/M8F723
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

Select appropriate tab below to view additional metadata details:

Project:

Project ID:PR001975
Project DOI:doi: 10.21228/M8F723
Project Title:Chronic manganese exposure disrupts glutamatergic signaling and alters behavior in APP/PSEN1 mice.
Project Type:Untargeted Metabolomics analysis
Project Summary:Pathological changes in Alzheimer’s disease (AD) begin decades before cognitive symptoms appear. Chronic exposure to environmental neurotoxins like manganese (Mn) from sources such as air pollution and water can impact disease development across decades. Mn toxicity can lead to motor and neuropsychiatric symptoms resembling Parkinson's disease, attributed to its accumulation in globus pallidus. In contrast, the impact of chronic lower-level exposures on normal and neuropathological brain function is unknown. We tested whether 10 months of a high Mn diet (2400 ppm) could alter aspects of glutamate signaling in APP/PSEN1 mice to further exacerbate cognitive impairments compared to control fed animals (70 ppm). This study supports the potential role for chronic environmental exposures in the development of Alzheimer’s disease associated neuropathology.
Institute:Vanderbilt University
Department:Chemistry
Laboratory:Center for Innovative Technology
Last Name:CODREANU
First Name:SIMONA
Address:1234 STEVENSON CENTER LANE
Email:SIMONA.CODREANU@VANDERBILT.EDU
Phone:6158758422

Subject:

Subject ID:SU003295
Subject Type:Mammal
Subject Species:Mus musculus
Taxonomy ID:APP/PSEN1 mice were originally obtained from Jackson Laboratories (#034833) and bred with C57Bl/6J mice (#000664).
Genotype Strain:APP/PSEN1 and WT
Age Or Age Range:12 months old
Gender:Male and female
Animal Animal Supplier:Jackson Laboratories

Factors:

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

mb_sample_id local_sample_id Sample source Sex Genotype Mn Treatment
SA343211C2nBrain-Cortex Female PS1 High
SA343212C3nBrain-Cortex Female PS1 High
SA343213C4nBrain-Cortex Female PS1 High
SA343214C2Brain-Cortex Female PS1 High
SA343215C1Brain-Cortex Female PS1 High
SA343216C1nBrain-Cortex Female PS1 High
SA343217C3Brain-Cortex Female PS1 High
SA343218C4Brain-Cortex Female PS1 High
SA343219C8nBrain-Cortex Female PS1 Low
SA343220C7nBrain-Cortex Female PS1 Low
SA343221C6nBrain-Cortex Female PS1 Low
SA343222C9nBrain-Cortex Female PS1 Low
SA343223C10nBrain-Cortex Female PS1 Low
SA343224C12nBrain-Cortex Female PS1 Low
SA343225C11nBrain-Cortex Female PS1 Low
SA343226C5nBrain-Cortex Female PS1 Low
SA343227C9Brain-Cortex Female PS1 Low
SA343228C7Brain-Cortex Female PS1 Low
SA343229C12Brain-Cortex Female PS1 Low
SA343230C11Brain-Cortex Female PS1 Low
SA343231C10Brain-Cortex Female PS1 Low
SA343232C6Brain-Cortex Female PS1 Low
SA343233C8Brain-Cortex Female PS1 Low
SA343234C5Brain-Cortex Female PS1 Low
SA343235C13nBrain-Cortex Female WT High
SA343236C14nBrain-Cortex Female WT High
SA343237C19nBrain-Cortex Female WT High
SA343238C19Brain-Cortex Female WT High
SA343239C15nBrain-Cortex Female WT High
SA343240C18Brain-Cortex Female WT High
SA343241C17Brain-Cortex Female WT High
SA343242C16Brain-Cortex Female WT High
SA343243C14Brain-Cortex Female WT High
SA343244C13Brain-Cortex Female WT High
SA343245C16nBrain-Cortex Female WT High
SA343246C17nBrain-Cortex Female WT High
SA343247C18nBrain-Cortex Female WT High
SA343248C15Brain-Cortex Female WT High
SA343249C24nBrain-Cortex Female WT Low
SA343250C22nBrain-Cortex Female WT Low
SA343251C25nBrain-Cortex Female WT Low
SA343252C20nBrain-Cortex Female WT Low
SA343253C21nBrain-Cortex Female WT Low
SA343254C23nBrain-Cortex Female WT Low
SA343255C26nBrain-Cortex Female WT Low
SA343256C27Brain-Cortex Female WT Low
SA343257C25Brain-Cortex Female WT Low
SA343258C26Brain-Cortex Female WT Low
SA343259C23Brain-Cortex Female WT Low
SA343260C24Brain-Cortex Female WT Low
SA343261C22Brain-Cortex Female WT Low
SA343262C20Brain-Cortex Female WT Low
SA343263C27nBrain-Cortex Female WT Low
SA343264C21Brain-Cortex Female WT Low
SA343265C32Brain-Cortex Male PS1 High
SA343266C30Brain-Cortex Male PS1 High
SA343267C31Brain-Cortex Male PS1 High
SA343268C28Brain-Cortex Male PS1 High
SA343269C29nBrain-Cortex Male PS1 High
SA343270C28nBrain-Cortex Male PS1 High
SA343271C32nBrain-Cortex Male PS1 High
SA343272C29Brain-Cortex Male PS1 High
SA343273C30nBrain-Cortex Male PS1 High
SA343274C31nBrain-Cortex Male PS1 High
SA343275C35Brain-Cortex Male PS1 Low
SA343276C35nBrain-Cortex Male PS1 Low
SA343277C36nBrain-Cortex Male PS1 Low
SA343278C37nBrain-Cortex Male PS1 Low
SA343279C34nBrain-Cortex Male PS1 Low
SA343280C33nBrain-Cortex Male PS1 Low
SA343281C34Brain-Cortex Male PS1 Low
SA343282C36Brain-Cortex Male PS1 Low
SA343283C37Brain-Cortex Male PS1 Low
SA343284C33Brain-Cortex Male PS1 Low
SA343285C43nBrain-Cortex Male WT High
SA343286C44nBrain-Cortex Male WT High
SA343287C45nBrain-Cortex Male WT High
SA343288C53nBrain-Cortex Male WT High
SA343289C42nBrain-Cortex Male WT High
SA343290C41nBrain-Cortex Male WT High
SA343291C39nBrain-Cortex Male WT High
SA343292C40nBrain-Cortex Male WT High
SA343293C38nBrain-Cortex Male WT High
SA343294C53Brain-Cortex Male WT High
SA343295C43Brain-Cortex Male WT High
SA343296C44Brain-Cortex Male WT High
SA343297C41Brain-Cortex Male WT High
SA343298C40Brain-Cortex Male WT High
SA343299C38Brain-Cortex Male WT High
SA343300C39Brain-Cortex Male WT High
SA343301C45Brain-Cortex Male WT High
SA343302C42Brain-Cortex Male WT High
SA343303C51nBrain-Cortex Male WT Low
SA343304C50nBrain-Cortex Male WT Low
SA343305C52nBrain-Cortex Male WT Low
SA343306C50Brain-Cortex Male WT Low
SA343307C51Brain-Cortex Male WT Low
SA343308C49nBrain-Cortex Male WT Low
SA343309C48nBrain-Cortex Male WT Low
SA343310C52Brain-Cortex Male WT Low
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Collection:

Collection ID:CO003288
Collection Summary:Following euthanasia by terminal anesthesia with isoflurane followed by decapitation, the brains were quickly removed and divided into two hemispheres. One hemisphere was dissected into distinct brain areas including cortex and snap frozen before long term storage at -80 ºC. The second hemisphere was immersion fixed in 4% paraformaldehyde for at least 24 hours before being placed in 30% sucrose for 24-72 hours and then moved to 1xPBS.
Collection Protocol Filename:Tissue_acquisition_Cortex.pdf
Sample Type:Brain cortex
Storage Conditions:-80℃

Treatment:

Treatment ID:TR003304
Treatment Summary:Mice were maintained on standard lab chow (Purina 5001) which contains 70 ppm Mn until 3 months of ages. Mice were then randomly allocated by cage to control (70 ppm; D17020702) or high (2400 ppm) Mn diets. Diets were formulated by Research Diets Inc. and comprised their normal control diet (D19080201) and differed only in the amount of Mn. Food levels were checked at least weekly and mice were weighed monthly to ensure normal growth.
Treatment Protocol Filename:Mice_and_dietary_treatment.pdf

Sample Preparation:

Sampleprep ID:SP003302
Sampleprep Summary:Cortex tissue samples were analyzed via liquid chromatography-high resolution tandem mass spectrometry (LC-HRMS and LC-HRMS/MS) using previously described methods. Briefly, harvested cortex tissue samples were thawed on ice and lysed in 500 µL ice-cold lysis buffer (1:1:2, acetonitrile: methanol: ammonium bicarbonate 0.1M, pH 8.0) followed by probe tip sonication and normalized via protein amount (100 µg) based on a bicinchoninic acid protein assay (Thermo Fisher Scientific, Waltham, MA). Deproteinization of individual samples was performed by addition of 800 µL of ice-cold methanol following the addition of isotopically labeled standards (phenylalanine-D8, biotin-D2 and lauryl carnitine-D3) to determine sample process variability. Precipitated proteins were centrifuged at 10,000 rpm for 10 min after overnight incubation at -80°C. Metabolite extracts were dried in vacuo and further purified via liquid-liquid extraction (LLE) method with tert-Butyl methyl ether (MTBE). The hydrophilic fraction of each sample extract was transferred into a new Eppendorf tube, dried in vacuo, and stored at -80°C until further use.
Sampleprep Protocol Filename:MS_Methods_Cortex.pdf
Processing Storage Conditions:-80℃
Extract Storage:-80℃

Combined analysis:

Analysis ID AN005213 AN005214
Analysis type MS MS
Chromatography type HILIC HILIC
Chromatography system Thermo Vanquish Thermo Vanquish
Column Waters ACQUITY UPLC BEH Amide (100 x 2.1mm,1.7um) Waters ACQUITY UPLC BEH Amide (100 x 2.1mm,1.7um)
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 peak intensity peak intensity

Chromatography:

Chromatography ID:CH003943
Chromatography Summary:Hydrophilic separation
Methods Filename:MS_Methods_Cortex.pdf
Instrument Name:Thermo Vanquish
Column Name:Waters ACQUITY UPLC BEH Amide (100 x 2.1mm,1.7um)
Column Temperature:30
Flow Gradient:30 min; 95%A, 5%B
Flow Rate:0.20 mL/min
Solvent A:90% water, 10% acetonitrile; 5mM Ammonium Formate, 0.1%FA
Solvent B:10% water, 90% acetonitrile; 5mM Ammonium Formate, 0.1%FA
Chromatography Type:HILIC

MS:

MS ID:MS004946
Analysis ID:AN005213
Instrument Name:Thermo Q Exactive HF hybrid Orbitrap
Instrument Type:Orbitrap
MS Type:ESI
MS Comments:MS were acquired in both, positive and negative modes Progenesis QI v.3.0 (Non-linear Dynamics, Newcastle, UK) was used to review, process and normalize the mass spectrometry data. The pooled QC sample was used to align all MS and MS/MS sample runs.
Ion Mode:POSITIVE
Analysis Protocol File:MS_Methods_Cortex.pdf
  
MS ID:MS004947
Analysis ID:AN005214
Instrument Name:Thermo Q Exactive HF hybrid Orbitrap
Instrument Type:Orbitrap
MS Type:ESI
MS Comments:MS were acquired in both, positive and negative modes Progenesis QI v.3.0 (Non-linear Dynamics, Newcastle, UK) was used to review, process and normalize the mass spectrometry data. The pooled QC sample was used to align all MS and MS/MS sample runs.
Ion Mode:NEGATIVE
Analysis Protocol File:MS_Methods_Cortex.pdf
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