Targeted Neurotransmitters Profiling Identifies Metabolic Signatures in Rat Brain by LC-MS/MS: Application in Insomnia, Depression and Alzheimer’s Disease

Abstract

Epidemiological, cross-sectional, and prospective studies have suggested that insomnia, Alzheimer’s disease (AD) and depression are mutually interacting conditions and frequently co-occur. The monoamine and amino acid neurotransmitter systems in central nervous system were involved in the examination of neurobiological processes of this symptom complex. However, few studies have reported systematic and contrastive discussion of different neurotransmitters (NTs) changing in these neurological diseases. Thus, it is necessary to establish a reliable analytical method to monitoring NTs and their metabolite levels in rat brain tissues for elucidating the differences in pathophysiology of these neurological diseases. A rapid, sensitive and reliable LC-MS/MS method was established for simultaneous determination of the NTs and their metabolites, including tryptophan (Trp), tyrosine (Tyr), serotonin (5-HT), 5-hydroxyindolacetic acid (5-HIAA), dopamine (DA), acetylcholine (ACh), norepinephrine (NE), glutamic acid (Glu), and γ-aminobutyric acid (GABA) in rat brain tissues. The mobile phase consisting of methanol and 0.01% formic acid in water was performed on an Inertsil EP C18 column, and the developed method was validated well. Results demonstrated that there were significant differences for 5-HT, DA, NE, Trp, Tyr and ACh between model and control group in all three models, and a Bayes linear discriminant function was established to distinguish these three kinds of nervous system diseases by DA, Tyr and ACh for their significant differences among control and three model groups. It could be an excellent strategy to provide perceptions into the similarity and differentia of mechanisms from the point of NTs’ changing in brain directly and a new method to distinguish insomnia, depression and AD from view of essence.

Role of Ovarian Hormones in the Modulation of Sleep in Females Across the Adult Lifespan

“…Finally, transdermal E2 improves sleep quality, reduces sleep latency, and decreases awakenings in postmenopausal women (47-65 years), especially those with insomnia ( 92 , 93 ). Given that sleep apnea/insomnia are risk factors for Alzheimer’s disease (AD) ( 94 , 95 ), attenuating risk at midlife can have important implications for women’s health. Thus, greater research attention paid to the potential role of E2/P in preventing sleep disorders at midlife is needed.…”

Study on the Multitarget Synergistic Effects of Kai-Xin-San against Alzheimer’s Disease Based on Systems Biology

“…Interestingly, GR or PR inhibited D-gal-and Aβ 25-35 -triggered augmentation of AChE, whereas KXS further intensified this effect (Figure 2(g)). Previous studies showed that the concentration of ACh was significantly reduced in the AD model with HPLC-MS/MS quantitative analysis [31]. It was suggested that KXS could ameliorate ACh loss (correlated with cognition impairment of AD) by suppressing the activity of AChE.…”

“…Six groups of AD rats were administered intragastrically with KXS (10.0 g/kg), GR (3.0 g/kg), PR (2.0 g/kg), PO (3.0 g/kg), AT (2.0 g/kg), and Hup A (0.027 mg/kg) once a day from the third week until the end of the experiment [25]. At the end of the fourth week, the stereotaxic injection of 4 μg Aβ [25][26][27][28][29][30][31][32][33][34][35] (1 μg/μL) was operated at the following coordinates: anteroposterior-3.5; mediolateral-+2.0; and dorsoventral-2.8 mm [26]. Two weeks later, the Morris water maze test was used for evaluation.…”

Construction and Analysis of Human Diseases and Metabolites Network

“…Till date, studies conducted on the role of metabolites in diseases have mainly focused on the drugs and metabolic pathways (Li et al, 2011), the diseases and metabolic pathways (Li et al, 2012), or the metabolome in a single disease (Gonzalez et al, 2018;Xu et al, 2018;Che et al, 2019). The research on the relationship between diseases and metabolites is still limited, despite the fact that metabolic diseases have become highly frequent.…”