Abstract
ObjectsTo explore the long-term influence of methamphetamine abuse on metabolomics character, with gas chromatography-mass spectrometry (GS-MS) technology, and the potential regulatory network using the bioinformatics method.MethodsForty withdrawal methamphetamine abusers (WMA) were recruited from Shanghai Gaojing Forced Isolation Detoxification Institute. Forty healthy controls (HC) were recruited from society. GS-MS technology was used to detect metabolic products in serum. A bioinformatics method was used to build a regulatory network. Q-PCR was used to detect the candidate gene expressions, and ELISA was used to detect the regulatory enzyme expressions.ResultsFour pathways were significantly changed in the MA compared to the HC: (1) the arginine synthesis pathway, (2) alanine, aspartic acid and glutamate metabolic pathway, (3) cysteine and methionine metabolic pathway, and (4) the ascorbate and aldarate pathway (enrichment analysis p < 0.05, Impactor factor > 0.2). When focusing on the ‘Alanine, aspartate, and glutamate metabolism’ pathway, a regulatory network was established, and the expression of candidate regulatory genes and enzymes was verified. It was found that the expression of DLG2 (Discs large MAGUK scaffold protein 2), PLA2G4 (Phospholipase A2 group IVE), PDE4D (Phosphodiesterase 4D), PDE4B (Phosphodiesterase 4B), and EPHB2 (Ephrin type-B receptor 2) were significantly different between the two groups (p < 0.05), However, after adjusting for age and BMI, only DLG2, PLA2G4, and EPHB2 remained significant (p < 0.05). The expression of enzymes was not significantly different (p > 0.05).ConclusionMethamphetamine abuse influences the metabolic process in the long term, and DLG2, PLA2G4, and EPHB2 may regulate the glutamate metabolism pathway.
Highlights
Methamphetamine (METH) is a widely abused addictive psychostimulant, which accounts for a considerable share of global disease burden
Four pathways were significantly changed in the MA compared to the healthy controls (HC): (1) the arginine synthesis pathway, (2) alanine, aspartic acid and glutamate metabolic pathway, (3) cysteine and methionine metabolic pathway, and (4) the ascorbate and aldarate pathway
It was found that the expression of DLG2 (Discs large MAGUK scaffold protein 2), PLA2G4 (Phospholipase A2 group IVE), PDE4D (Phosphodiesterase 4D), PDE4B (Phosphodiesterase 4B), and EPHB2 (Ephrin type-B receptor 2) were significantly different between the two groups (p < 0.05), after adjusting for age and BMI, only DLG2, PLA2G4, and EPHB2 remained significant (p < 0.05)
Summary
Methamphetamine (METH) is a widely abused addictive psychostimulant, which accounts for a considerable share of global disease burden. Long-term abuse of METH causes serious physical and mental damage. METH is better at penetrating the center nervous system (CNS) and has a longer duration of action (Yang X. et al, 2018), making METH more addictive while the damage to the CNS is more serious and persistent. METH addicts often suffer from permanent psychotic symptoms (Mellsop et al, 2019) and cognitive decline, even when deprived from drugs, bringing great difficulties for patients who try to return to society. These symptoms are mostly attributed to METH-induced long-term neurotoxicity and excitotoxicity (Ashok et al, 2017). A previous study found that methamphetamine may result in glutamine system disturbance (Tasic et al, 2017), and glutamate + glutamine in the right inferior frontal cortex is decreased in methamphetamine users (Zheng et al, 2016)
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