Free Amino Acid Levels in Brain Cortex Tissues of Three Mouse Models with Alzheimer's Disease as Their N(O,S)-Ethoxycarbonyl/ tert-Butyldimethylsilyl Derivatives

摘要

The amino acids (AAs) such as aspartic acid, glutamic acid, (gamma)-aminobutyric acid (GABA) and 3,4-dihydroxyphenylalanine (DOPA) are known to act as neurotransmitters in the central nervous system [1,2]. The progressive cognitive decline and behavioral disturbances characterized by Alzheimer's disease (AD) patients have been explained as neurochemical alterations of multiple neurotransmitters systems in brain tissue [1, 2]. Therefore their accurate detection and measurement has become an important task in the study of etiology or progression of AD and other human neurodegenerative diseases. The present investigation was undertaken to measure the levels of free amino acids in brain cortex specimens from three 18 month old Tg2576 transgenic mice with AD as the AD model [3] and of three age-matched non-transgenic littermate mice as the control model. The two-phase ethoxycarbonyl (EOC) reaction conducted in one-step in strong alkaline solution [4] was modified into two-step pH shift mode (initially at pH 8 then raised to pH 12) for the simultaneous analysis of nineteen AAs including DOPA as their EOC/TBDMS derivatives by gas chromatography (GC) and GC combined with mass spectrometry (MS). The quantitative differences in the amino acid levels between control and AD mice were expressed as star patterns [5].