Ultrahigh-Performance Liquid Chromatography-High-Resolution Mass Spectrometry 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 the degeneration of motor and nonmotor circuitries. 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 proinflammatory 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 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 triacylglycerol (TG) and diacylglycerol (DG) expressions 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 immunotherapy is positively modifying the disease state.