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Proteomics and weighted gene correlated network analysis reveal glutamatergic synapse signaling in diazepam treatment of alcohol withdrawal.
Kong, Wan; Huang, Shanqing; Chen, Zikai; Li, Xiaolin; Liu, Shujing; Zhang, Zi; Yang, Ye; Wang, Zhanzhang; Zhu, Xiuqing; Ni, Xiaojia; Lu, Haoyang; Zhang, Ming; Li, Zezhi; Wen, Yuguan; Shang, Dewei.
Afiliación
  • Kong W; Department of Pharmacy, The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, China.
  • Huang S; Department of Pharmacy, The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, China.
  • Chen Z; Department of Administration, The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, China.
  • Li X; Department of Pharmacy, The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, China.
  • Liu S; Department of Pharmacy, The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, China.
  • Zhang Z; Department of Pharmacy, The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, China.
  • Yang Y; Department of Pharmacy, The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, China.
  • Wang Z; Department of Pharmacy, The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, China.
  • Zhu X; Department of Pharmacy, The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, China.
  • Ni X; Department of Pharmacy, The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, China.
  • Lu H; Department of Pharmacy, The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, China.
  • Zhang M; Department of Pharmacy, The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, China.
  • Li Z; Department of Adult Psychiatry, The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, China.
  • Wen Y; Department of Pharmacy, The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, China.
  • Shang D; Department of Pharmacy, The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, China.
Front Pharmacol ; 13: 1111758, 2022.
Article en En | MEDLINE | ID: mdl-36712652
Background: Alcohol use disorder (AUD) is characterized by chronic excessive alcohol consumption, often alternating with periods of abstinence known as alcohol withdrawal syndrome (AWS). Diazepam is the preferred benzodiazepine for treatment of alcohol withdrawal syndrome under most circumstances, but the specific mechanism underlying the treatment needs further research. Methods: We constructed an animal model of two-bottle choices and chronic intermittent ethanol exposure. LC-MS/MS proteomic analysis based on the label-free and intensity-based quantification approach was used to detect the protein profile of the whole brain. Weighted gene correlated network analysis was applied for scale-free network topology analysis. We established a protein-protein interaction network based on the Search Tool for the Retrieval of Interacting Genes (STRING) database and Cytoscape software and identified hub proteins by CytoHubba and MCODE plugins of Cytoscape. The online tool Targetscan identified miRNA-mRNA pair interactions. Results: Seven hub proteins (Dlg3, Dlg4, Shank3, Grin2b, Camk2b, Camk2a and Syngap1) were implicated in alcohol withdrawal syndrome or diazepam treatment. In enrichment analysis, glutamatergic synapses were considered the most important pathway related to alcohol use disorder. Decreased glutamatergic synapses were observed in the late stage of withdrawal, as a protective mechanism that attenuated withdrawal-induced excitotoxicity. Diazepam treatment during withdrawal increased glutamatergic synapses, alleviating withdrawal-induced synapse inhibition. Conclusion: Glutamatergic synapses are considered the most important pathway related to alcohol use disorder that may be a potential molecular target for new interventional strategies.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Front Pharmacol Año: 2022 Tipo del documento: Article País de afiliación: China Pais de publicación: Suiza
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Front Pharmacol Año: 2022 Tipo del documento: Article País de afiliación: China Pais de publicación: Suiza