Transgenic Parkinson's Mice Following Immunotherapy
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ABSTRACT: An UHPLC-HRMS Metabolomics and Lipidomics Study of Stool from Transgenic Parkinson's disease Mice Following Immunotherapy. Parkinson’s disease (PD) is characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta of the brain as well as degeneration of motor and non-motor circuitry. The cause of neuronal death is currently unknown, although chronic neuroinflammation, aggregated α-synuclein, mitochondrial dysfunction and oxidative stress have all been implicated. Gliosis has been shown to exacerbate neuroinflammation via secretion of pro-inflammatory cytokines, and there is a subsequent infiltration of T lymphocytes (T-cells), into the brain of PD patients. Using liquid chromatography-high resolution mass spectrometry (LC-HRMS), we have observed metabolomic changes in stool samples, thought to be associated with the potential disease-modifying effect of an immunotherapy administered to transgenic Parkinsonian (A53T) mice. Significant elevations (p<0.05) in metabolites associated with immune response (taurine, histamine and its methylated product, 3-methylhistamine) are identified as being higher in the mice undergoing immunotherapy. Furthermore, a reduction in triacylglycerols (TG) and diacylglyceols (DG) expression in stool following immunotherapy suggests a regulation of lipid breakdown or biosynthesis with the vaccine. These “omics” markers (among others reported in this article) along with weight gain and increased life expectancy suggest that the immunotherapy is positively modifying the disease state.
ORGANISM(S): Mouse Mus Musculus
TISSUE(S): Feces
DISEASE(S): Parkinsons Disease
SUBMITTER: Emily Gill
PROVIDER: ST001281 | MetabolomicsWorkbench | Wed Oct 23 00:00:00 BST 2019
REPOSITORIES: MetabolomicsWorkbench
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