Summary of Study ST004071

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 PR002556. The data can be accessed directly via it's Project DOI: 10.21228/M8824K 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.

Study ID	ST004071
Study Title	Metabolic perturbation in ependymal cells leads to local and distant neurodegeneration and cognitive decline - Study 2 of 3 (12-month Glut1KO against Ctrl)
Study Summary	Ependymal cells (ECs) are specialized multi-ciliated glial cells that line the ventricular system of the brain, regulating cerebrospinal fluid flow (CSF) and the neighbouring neural stem cell (NSC) niche. However, their role in maintaining brain homeostasis or in disease pathogenesis remains unclear. To elucidate their function, we disrupted ependymal glucose metabolism by genetically deleting glucose-transporter-1 (GLUT1/Slc2a1) in postnatal ECs. Analyses were carried out across three separate studies (batches), with one study at 1 month (6 mice) and two studies at 12 months (3 mice, 5 mice). Results from this project confirm CSF flow changes and disrupted NSC differentiation and neuroblast migration. These mice also exhibited periventricular lipid droplet accumulation similar to Alzheimer’s disease brains. Aged cKO mice exhibited progressive cognitive and motor dysfunction, and onset of seizure activity. These behavioral deficits were coincident with various neurodegenerative pathologies, including dysmyelination, microglia-associated inflammation, and lipid imbalance. When combined with metabolic perturbation in ECs, 5xFAD mice exhibited accelerated disease onset. These findings suggest that ECs are important regulators of brain homeostasis, and their dysfunction may contribute to the pathogenesis of neurodegenerative diseases. In this part, 5x mice were analyzed at 12-months under Glut1ko (2 mice) or Control (3 mice) conditions. This study was conducted to append the number of replicates from study 1 at 12 months.
Institute	University of Calgary
Department	Veterinary Medicine
Laboratory	Biernaskie Lab
Last Name	Colter
First Name	James
Address	2500 University Drive NW, Calgary AB Canada, T2N1N4
Email	jdcolter@ucalgary.ca
Phone	+1 (403) 210-7306
Submit Date	2025-06-14
Num Groups	4
Total Subjects	13
Study Comments	Part 2 of 3
Publications	(under review)
Raw Data Available	Yes
Raw Data File Type(s)	mcf
Analysis Type Detail	MALDI-MS
Release Date	2025-08-15
Release Version	1

Select appropriate tab below to view additional metadata details:

Project:

Project ID:	PR002556
Project DOI:	doi: 10.21228/M8824K
Project Title:	Metabolic perturbation in ependymal cells leads to local and distant neurodegeneration and cognitive decline
Project Type:	MS Imaging Analysis
Project Summary:	Ependymal cells (ECs) are specialized multi-ciliated glial cells that line the ventricular system of the brain, regulating cerebrospinal fluid flow (CSF) and the neighbouring neural stem cell (NSC) niche. However, their role in maintaining brain homeostasis or in disease pathogenesis remains unclear. To elucidate their function, we disrupted ependymal glucose metabolism by genetically deleting glucose-transporter-1 (GLUT1/Slc2a1) in postnatal ECs. Analyses were carried out across three separate studies (batches), with one study at 1 month (6 mice) and two studies at 12 months (3 mice, 5 mice). Results from this project confirm CSF flow changes and disrupted NSC differentiation and neuroblast migration. These mice also exhibited periventricular lipid droplet accumulation similar to Alzheimer’s disease brains. Aged cKO mice exhibited progressive cognitive and motor dysfunction, and onset of seizure activity. These behavioral deficits were coincident with various neurodegenerative pathologies, including dysmyelination, microglia-associated inflammation, and lipid imbalance. When combined with metabolic perturbation in ECs, 5xFAD mice exhibited accelerated disease onset. These findings suggest that ECs are important regulators of brain homeostasis, and their dysfunction may contribute to the pathogenesis of neurodegenerative diseases.
Institute:	University of Calgary
Department:	Veterinary Medicine
Laboratory:	Biernaskie Lab
Last Name:	Colter
First Name:	James
Address:	2500 University Drive NW
Email:	jdcolter@ucalgary.ca
Phone:	+1 (403) 210-7306
Funding Source:	CIHR
Project Comments:	Part 1 of 3
Publications:	(Under Review)
Contributors:	Nilesh Sharma, Alexander Pun, James Colter, Leslie Cao, Nicole Rosin, Dominic Gerding, Isabel Rea, Apolline Pistek, Qandeel Shafqat, Sarthak Sinha, Elodie Labit, Eren Kutluberk, Caleb Small, Reese Landes, Tak Ho Chu, Kartikeya Murari, E. Dale Abel, Jeffrey T. Joseph, Rehana Leak, Jeff Dunn, and Jeff Biernaskie

Subject:

Subject ID:	SU004217
Subject Type:	Mammal
Subject Species:	Mus musculus
Taxonomy ID:	10090
Age Or Age Range:	12 months

Factors:

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

mb_sample_id	local_sample_id	Sample source	Condition	Sample source
SA472705	162	220927_secondset	Control	Brain
SA472706	163	220927_secondset	Control	Brain
SA472707	164	220927_secondset	Control	Brain
SA472708	272	220927_secondset	Knockout	Brain
SA472709	292	220927_secondset	Knockout	Brain

Showing results 1 to 5 of 5

Showing results 1 to 5 of 5

Collection:

Collection ID:	CO004210
Collection Summary:	The brain was collected as mentioned below. After the mice were euthanized, it was transcardially perfused with PBS. The brain is dissected out and then flash frozen in liquid nitrogen. The flash frozen brain tissue was then sectioned at 12 μm thickness on a cryostat (Leica Biosystems).
Sample Type:	Brain

Treatment:

Treatment ID:	TR004226
Treatment Summary:	The brain was collected as mentioned above with minor modifications. After the mice were euthanized, it was transcardially perfused with PBS. The brain is dissected out and then flash frozen in liquid nitrogen. The flash frozen brain tissue was then sectioned at 12 μm thickness on a cryostat (Leica Biosystems). MALDI matrix (9-aminoacridine, 9AA) (Sigma-Aldrich) was spray-coated onto the target slides in an automated fashion using a TM Sprayer (HTX Imaging). 9-AA was made up as a 5 mg/ml solution in 90% methanol. Four passes were used with a nozzle temperature of 85°, a flowrate of 0.15 ml/min, 2-mm track spacing, and a stage velocity of 700 mm/min. Nitrogen was used as the nebulization gas and was set to 10 psi. Images were acquired on a 15T Fourier transform ion cyclotron resonance mass spectrometer (FT-ICR MS, Solarix, Bruker Daltonics) equipped with an Apollo II dual ion source and Smartbeam II 2kHz Nd:YAG laser that was frequency tripled to 355 nm. Data were collected in the negative ion mode with the laser operating at 2 kHz at 50 μm resolution. Tentative metabolite identifications were made by accurate mass, typically better than 1 ppm. Images were analyzed with flexImaging software (Bruker), while average spectra were exported to mMass for visualization of differences.

Treatment ID:

TR004226

Treatment Summary:

The brain was collected as mentioned above with minor modifications. After the mice were euthanized, it was transcardially perfused with PBS. The brain is dissected out and then flash frozen in liquid nitrogen. The flash frozen brain tissue was then sectioned at 12 μm thickness on a cryostat (Leica Biosystems). MALDI matrix (9-aminoacridine, 9AA) (Sigma-Aldrich) was spray-coated onto the target slides in an automated fashion using a TM Sprayer (HTX Imaging). 9-AA was made up as a 5 mg/ml solution in 90% methanol. Four passes were used with a nozzle temperature of 85°, a flowrate of 0.15 ml/min, 2-mm track spacing, and a stage velocity of 700 mm/min. Nitrogen was used as the nebulization gas and was set to 10 psi. Images were acquired on a 15T Fourier transform ion cyclotron resonance mass spectrometer (FT-ICR MS, Solarix, Bruker Daltonics) equipped with an Apollo II dual ion source and Smartbeam II 2kHz Nd:YAG laser that was frequency tripled to 355 nm. Data were collected in the negative ion mode with the laser operating at 2 kHz at 50 μm resolution. Tentative metabolite identifications were made by accurate mass, typically better than 1 ppm. Images were analyzed with flexImaging software (Bruker), while average spectra were exported to mMass for visualization of differences.

Sample Preparation:

Sampleprep ID:	SP004223
Sampleprep Summary:	MALDI matrix (9-aminoacridine, 9AA) (Sigma-Aldrich) was spray-coated onto the target slides in an automated fashion using a TM Sprayer (HTX Imaging). 9-AA was made up as a 5 mg/ml solution in 90% methanol. Four passes were used with a nozzle temperature of 85°, a flowrate of 0.15 ml/min, 2-mm track spacing, and a stage velocity of 700 mm/min. Nitrogen was used as the nebulization gas and was set to 10 psi. Images were acquired on a 15T Fourier transform ion cyclotron resonance mass spectrometer (FT-ICR MS, Solarix, Bruker Daltonics) equipped with an Apollo II dual ion source and Smartbeam II 2kHz Nd:YAG laser that was frequency tripled to 355 nm. Data were collected in the negative ion mode with the laser operating at 2 kHz at 50 μm resolution. Tentative metabolite identifications were made by accurate mass, typically better than 1 ppm. Images were analyzed with flexImaging software (Bruker), while average spectra were exported to mMass for visualization of differences.

Sampleprep ID:

SP004223

Sampleprep Summary:

MALDI matrix (9-aminoacridine, 9AA) (Sigma-Aldrich) was spray-coated onto the target slides in an automated fashion using a TM Sprayer (HTX Imaging). 9-AA was made up as a 5 mg/ml solution in 90% methanol. Four passes were used with a nozzle temperature of 85°, a flowrate of 0.15 ml/min, 2-mm track spacing, and a stage velocity of 700 mm/min. Nitrogen was used as the nebulization gas and was set to 10 psi. Images were acquired on a 15T Fourier transform ion cyclotron resonance mass spectrometer (FT-ICR MS, Solarix, Bruker Daltonics) equipped with an Apollo II dual ion source and Smartbeam II 2kHz Nd:YAG laser that was frequency tripled to 355 nm. Data were collected in the negative ion mode with the laser operating at 2 kHz at 50 μm resolution. Tentative metabolite identifications were made by accurate mass, typically better than 1 ppm. Images were analyzed with flexImaging software (Bruker), while average spectra were exported to mMass for visualization of differences.

Chromatography:

Chromatography ID:	CH005119
Instrument Name:	none
Column Name:	none
Column Temperature:	none
Flow Gradient:	none
Flow Rate:	none
Solvent A:	none
Solvent B:	none
Chromatography Type:	None (Direct infusion)

Analysis:

Analysis ID:	AN006737
Analysis Type:	MS
Chromatography ID:	CH005119
Num Factors:	2
Num Metabolites:	149
Units:	n/a