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:10090
Genotype Strain:APP/PSEN1 and WT
Age Or Age Range:12 months old
Gender:Male and female
Animal Animal Supplier:Jackson Laboratories
Species Group:Mammals

Factors:

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

mb_sample_id local_sample_id Sex Genotype Mn Treatment
SA343211C2nFemale PS1 High
SA343212C3nFemale PS1 High
SA343213C4nFemale PS1 High
SA343214C2Female PS1 High
SA343215C1Female PS1 High
SA343216C1nFemale PS1 High
SA343217C3Female PS1 High
SA343218C4Female PS1 High
SA343219C8nFemale PS1 Low
SA343220C7nFemale PS1 Low
SA343221C6nFemale PS1 Low
SA343222C9nFemale PS1 Low
SA343223C10nFemale PS1 Low
SA343224C12nFemale PS1 Low
SA343225C11nFemale PS1 Low
SA343226C5nFemale PS1 Low
SA343227C9Female PS1 Low
SA343228C7Female PS1 Low
SA343229C12Female PS1 Low
SA343230C11Female PS1 Low
SA343231C10Female PS1 Low
SA343232C6Female PS1 Low
SA343233C8Female PS1 Low
SA343234C5Female PS1 Low
SA343235C13nFemale WT High
SA343236C14nFemale WT High
SA343237C19nFemale WT High
SA343238C19Female WT High
SA343239C15nFemale WT High
SA343240C18Female WT High
SA343241C17Female WT High
SA343242C16Female WT High
SA343243C14Female WT High
SA343244C13Female WT High
SA343245C16nFemale WT High
SA343246C17nFemale WT High
SA343247C18nFemale WT High
SA343248C15Female WT High
SA343249C24nFemale WT Low
SA343250C22nFemale WT Low
SA343251C25nFemale WT Low
SA343252C20nFemale WT Low
SA343253C21nFemale WT Low
SA343254C23nFemale WT Low
SA343255C26nFemale WT Low
SA343256C27Female WT Low
SA343257C25Female WT Low
SA343258C26Female WT Low
SA343259C23Female WT Low
SA343260C24Female WT Low
SA343261C22Female WT Low
SA343262C20Female WT Low
SA343263C27nFemale WT Low
SA343264C21Female WT Low
SA343265C32Male PS1 High
SA343266C30Male PS1 High
SA343267C31Male PS1 High
SA343268C28Male PS1 High
SA343269C29nMale PS1 High
SA343270C28nMale PS1 High
SA343271C32nMale PS1 High
SA343272C29Male PS1 High
SA343273C30nMale PS1 High
SA343274C31nMale PS1 High
SA343275C35Male PS1 Low
SA343276C35nMale PS1 Low
SA343277C36nMale PS1 Low
SA343278C37nMale PS1 Low
SA343279C34nMale PS1 Low
SA343280C33nMale PS1 Low
SA343281C34Male PS1 Low
SA343282C36Male PS1 Low
SA343283C37Male PS1 Low
SA343284C33Male PS1 Low
SA343285C43nMale WT High
SA343286C44nMale WT High
SA343287C45nMale WT High
SA343288C53nMale WT High
SA343289C42nMale WT High
SA343290C41nMale WT High
SA343291C39nMale WT High
SA343292C40nMale WT High
SA343293C38nMale WT High
SA343294C53Male WT High
SA343295C43Male WT High
SA343296C44Male WT High
SA343297C41Male WT High
SA343298C40Male WT High
SA343299C38Male WT High
SA343300C39Male WT High
SA343301C45Male WT High
SA343302C42Male WT High
SA343303C51nMale WT Low
SA343304C50nMale WT Low
SA343305C52nMale WT Low
SA343306C50Male WT Low
SA343307C51Male WT Low
SA343308C49nMale WT Low
SA343309C48nMale WT Low
SA343310C52Male 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℃

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

Analysis:

Analysis ID:AN005213
Analysis Type:MS
Analysis Protocol File:MS_Methods_Cortex.pdf
Chromatography ID:CH003943
Has Mz:1
Has Rt:1
Rt Units:Minutes
Results File:ST003176_AN005213_Results.txt
Units:peak intensity
  
Analysis ID:AN005214
Analysis Type:MS
Analysis Protocol File:MS_Methods_Cortex.pdf
Chromatography ID:CH003943
Has Mz:1
Has Rt:1
Rt Units:Minutes
Results File:ST003176_AN005214_Results.txt
Units:peak intensity
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