Summary of project PR002556
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
| 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 |
Summary of all studies in project PR002556
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST004070 | Metabolic perturbation in ependymal cells leads to local and distant neurodegeneration and cognitive decline - Study 1 of 3 (12-month Glut1KO against Ctrl) | Mus musculus | University of Calgary | MS | 2025-08-15 | 1 | 3 | Uploaded data (10.5G)* |
| ST004071 | Metabolic perturbation in ependymal cells leads to local and distant neurodegeneration and cognitive decline - Study 2 of 3 (12-month Glut1KO against Ctrl) | Mus musculus | University of Calgary | MS | 2025-08-15 | 1 | 5 | Uploaded data (13.1G)* |
| ST004072 | Metabolic perturbation in ependymal cells leads to local and distant neurodegeneration and cognitive decline - Study 3 of 3 (1-month Glut1KO against Ctrl) | Mus musculus | University of Calgary | MS | 2025-08-15 | 1 | 6 | Uploaded data (38.3G)* |
