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Determination of neurotransmitters in hippocampus of AD rats induced by Aβ25-35 based on UHPLC-TQ-MS

Tianyi Xu  Zhongying Liu  Jingrong Liu  Ying Huang  Yanli Liu  Yuanyuan Liu  Mengying Wei  Zhiqiang Liu  
【摘要】:Alzheimer's disease(AD) as the most prevalent form of dementia is a neurodegenerative disease. It has become one of the most consuming diseases in society. In 2017, 7 million Americans older than 65 years old died with AD costing an estimated 18.4 billion hours and more than $232 billion for care. The pathogenesis of AD is still not clarified completely at present. It mainly includes the accumulation of extracellular beta amyloid peptide, and the intracellular neurofibrillary tangles to make up of the hyperphosphorylated tau protein aggregates, functional cholinergic damage, oxidative stress-mediated mitochondrial signaling cascade, glutamate mediated excitotoxicity, gene mutation, neurodegeneration, the abnormal functioning of different neurotransmitters and so on. AD pathology has been reported to be related to dopaminergic, GABAergic,cholinergic, glutamatergic and serotonergic system disturbances in the brain. Ultrahigh performance liquid chromatographytriple quadrupole mass spectrometry(UHPLC-TQ-MS) in multiple reactions monitoring(MRM) mode provides significant advantages in signal-to-noise ratio, selectivity, sensitivity and resolution, so it was chosen to determine the 9 neurotransmitter contents of hippocampus in this study. The results showed that, compared with healthy control group, the levels of serotonin, norepinephrine, dopamine, taurine, acetylcholine, glycine and γ-aminobutyric acid in the hippocampus of AD rats at 8 weeks significantly decreased, and the contents of aspartic acid and glutamate significantly increased. The results showed that all of the 9 detected neurotransmitters were involved in the pathogenesis of β-amyloid 25–35 induced AD model.

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