Summary of project PR000693
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 PR000693. The data can be accessed directly via it's Project DOI: 10.21228/M83H4H This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Project ID: | PR000693 |
| Project DOI: | doi: 10.21228/M83H4H |
| Project Title: | Mayo Pilot and Feasibility: The pathogenic NMO IgG dysregulates the astrocytic glutamine-glutamate cycle: a metabolic basis for depression in NMO patients |
| Project Summary: | Neuromyelitis optica (NMO) is a disabling central nervous system (CNS) inflammatory disorder that involves a pathogenic autoantibody (NMO IgG) directed against aquaporin-4, the major brain water channel, expressed on astrocytes. Astrocytes in brain tissue from patients with NMO exhibit a spectrum of abnormalities and pathologies ranging from sublytic gliosis and reactivity to outright destruction. Our current working model for NMO pathogenesis involves an early and robust NMO IgG-induced astrocytic stress response that drives metabolic dyshomeostasis and the production of pro-inflammatory cytokines and chemokines that amplify pathology by recruiting innate immune effector cells to the CNS. Notably, astrocytes are implicated in clinical depression and patients with NMO experience depression at levels that exceed the general population. Preliminary magnetic resonance spectroscopy data from our group indicates that glutamate levels are reduced in the prefrontal cortex of NMO patients, suggesting that unipolar depression in these individuals is a direct pathogenic effect of NMO IgG-induced astrocytic dysregulation. Because astrocytes are critical for glutamine-glutamate cycling in the CNS, we hypothesize that stimulation of primary astrocytes with patient-derived NMO IgG will drive a metabolic shift marked by alterations in cellular levels of glutamate and glutamine. In preliminary experiments using 1H-NMR to measure metabolic changes induced in astrocytes by stimulation with NMO IgG we observed variable glutamate and glutamine responses. To overcome issues of signal-to-noise and the high basal levels of glutamate and glutamine produced by astrocytes, we now propose to use isotopic tracing and 13C-NMR to quantify NMO IgG-induced metabolic dysregulation. Our ultimate goal is to use NMO IgG-induced dyshomeostasis as a microscope to reveal basic mechanisms of pathogenic glutamate-glutamine metabolism in astrocytes that may not only impact the health of patients with NMO but may also yield novel insights into the mechanisms of depression in general. |
| Institute: | Mayo Clinic |
| Last Name: | Howe |
| First Name: | Charles |
| Address: | 200 First St. SW, Rochester, Minnesota, 55905, USA |
| Email: | howe@mayo.edu |
| Phone: | 507-284-9288 |
Summary of all studies in project PR000693
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST001035 | TCA Isotopomers in Neuromyelitis Optica Patients (part - I) | Homo sapiens | Mayo Clinic | MS | 2020-08-20 | 1 | 108 | Not available |
| ST001036 | TCA Concentrations in Neuromyelitis Optica Patients (part - II) | Homo sapiens | Mayo Clinic | MS | 2020-08-20 | 1 | 51 | Not available |
