Study on Urine Metabolic Profile of Aβ25–35-Induced Alzheimer's Disease Using UHPLC-Q-TOF-MS. (1st December 2018)

• Record Type: Journal Article
• Authors: Liu, Yuanyuan; Wei, Mengying; Yue, Kexin; Hu, Mingxin; Li, Shizhe; Men, Lihui; Pi, Zifeng; Liu, Zhiqiang; Liu, Zhongying
• Is Part Of: Neuroscience. Volume 394(2018)
• Page Start: 30
• Page End: 43
• Publication Date: 2018-12-01
• Subjects: 5-HT serotonin -- Ach acetylcholine -- AD Alzheimer's disease -- Asp aspartic acid -- Aβ 25–35 β-amyloid 25–35 -- DA dopamine -- GABA γ-aminobutyric acid -- Glu glutamate -- Gly glycine -- HE hematoxylin and eosin -- IOD integral optical densities -- MRM multiple reactions monitoring -- MWM Morris water maze -- NE norepinephrine -- OPLS-DA orthogonal partial least squares discriminant analysis -- PCA principal component analysis -- p-tau hyperphosphorylated tau -- QC quality control -- Tau taurine -- UHPLC-Q-TOF-MS ultrahigh performance liquid chromatography quadrupole time-of-flight mass spectrometry -- UHPLC-TQ-MS ultrahigh performance liquid chromatography–triple quadrupole mass spectrometry; Aβ25–35 -- Alzheimer's disease -- UHPLC-Q-TOF-MS -- UHPLC-TQ-MS -- neurotransmitters -- urinary metabolomics; Neurochemistry -- Periodicals; Neurophysiology -- Periodicals; Neurology -- Periodicals; Neurochimie -- Périodiques; Neurophysiologie -- Périodiques; Neurochemistry; Neurophysiology; Electronic journals; Periodicals; Electronic journals; 612.8
• DOI: 10.1016/j.neuroscience.2018.10.001
• Languages: English
• ISSNs: 0306-4522

Abstract

Highlights: An Aβ25–35-induced AD model developed on Sprague–Dawley rats was successfully established at 8 weeks after surgery. The content of 9 neurotransmitters in the hippocampus of AD rats changed significantly. 45 endogenous metabolites mainly involved in 8 metabolic pathways were identified as potential biomarkers related to AD. The pathogenesis of AD was due to gut microbiome dysbiosis, inhibition of energy metabolism and oxidative stress injury. Abstract: Alzheimer's disease (AD) is a progressive neurodegenerative disorder, with no effective method for its treatment so far. The pathogenesis of AD has been reported, but the endogenous metabolic profile and disease-related biomarkers are still not clear. To better understand AD, an AD model induced by injecting β-amyloid 25–35 (Aβ 25–35) solution into bilateral hippocampus was developed on Sprague–Dawley rats. After 8 weeks of modeling, the impairment of spatial learning and memory ability in AD rats were assessed by Morris water maze task. Hematoxylin and eosin staining and immunohistochemistry were used to investigate the pathological changes of hippocampus. The neurotransmitter concentrations in the hippocampus were measured using UHPLC-TQ-MS. Urinary metabolomics based on UHPLC-Q-TOF-MS was established to delineate the alterations of endogenous metabolites in AD rats. The results showed that compared with healthy control rats, AD rats suffered from cognitive dysfunction, hippocampus damage, Aβ formation and tau phosphorylation at 8 weeks after surgery, suggesting that the Aβ25–35-induced AD model was successfully established. In addition, the levels of γ-aminobutyric acid, acetylcholine, glycine, norepinephrine, serotonin, taurine and dopamine decreased and glutamate and aspartic acid increased in hippocampal tissue of AD rats. 45 altered metabolites mainly involved in 8 metabolic pathways were identified as the endogenous biomarkers of AD. According to the analysis of the biological significance of metabolic profiles, the pathogenesis of AD was mainly due to gut microbiome dysbiosis, inhibition of energy metabolism, oxidative stress injury and loss of neuronal protective substances.