AUTHOR=Peng Sufang , Su Hang , Chen Tianzhen , Li Xiaotong , Du Jiang , Jiang Haifeng , Zhao Min 

TITLE=The Potential Regulatory Network of Glutamate Metabolic Pathway Disturbance in Chinese Han Withdrawal Methamphetamine Abusers

JOURNAL=Frontiers in Genetics

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2021.653443

DOI=10.3389/fgene.2021.653443

ISSN=1664-8021

ABSTRACT=<sec><title>Objects</title><p>To 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.</p></sec><sec><title>Methods</title><p>Forty 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.</p></sec><sec><title>Results</title><p>Four 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 <italic>p</italic> &lt; 0.05, Impactor factor &gt; 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 <italic>DLG2</italic> (Discs large MAGUK scaffold protein 2), <italic>PLA2G4</italic> (Phospholipase A2 group IVE), <italic>PDE4D</italic> (Phosphodiesterase 4D), <italic>PDE4B</italic> (Phosphodiesterase 4B), and <italic>EPHB2</italic> (Ephrin type-B receptor 2) were significantly different between the two groups (<italic>p</italic> &lt; 0.05), However, after adjusting for age and BMI, only <italic>DLG2, PLA2G4</italic>, and <italic>EPHB</italic>2 remained significant (<italic>p</italic> &lt; 0.05). The expression of enzymes was not significantly different (<italic>p</italic> &gt; 0.05).</p></sec><sec><title>Conclusion</title><p>Methamphetamine abuse influences the metabolic process in the long term, and <italic>DLG2, PLA2G4</italic>, and <italic>EPHB2</italic> may regulate the glutamate metabolism pathway.</p></sec>