Samuel J. Mabry, Xixi Cao, Yanqi Zhu, Caleb Rowe, Shalin Patel, Camila González-Arancibia, Tiziana Romanazzi, David P. Saleeby, Anna Elam, Hui-Ting Lee, Serhat Turkmen, Shelby N. Lauzon, Cesar E. Hernandez, HaoSheng Sun, Hui Wu, Angela M. Carter, Aurelio Galli
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引用次数: 0
Abstract
Amphetamines are psychostimulants that are commonly used to treat neuropsychiatric disorders and are prone to misuse. The pathogenesis of amphetamine use disorder (AUD) is associated with dysbiosis (an imbalance in the body’s microbiome) and bacterially produced short-chain fatty acids (SCFAs), which are implicated in the gut-brain axis. Amphetamine exposure in both rats and humans increases the amount of intestinal Fusobacterium nucleatum, which releases SFCAs. Here, we found that colonization of gnotobiotic Drosophila melanogaster with F. nucleatum or supplementing the flies’ diet with the SCFA butyrate enhanced the psychomotor and reward properties of amphetamine. Butyrate inhibits histone deacetylases (HDACs), and knockdown of HDAC1 recapitulated the effects induced by F. nucleatum or butyrate. The enhancement in amphetamine-induced behaviors was mediated by an increase in the amount of released dopamine that resulted from amphetamine-induced reversal of dopamine transporter (DAT) function, termed nonvesicular dopamine release (NVDR). The magnitude of amphetamine-induced NVDR was partially mediated by an increase in DAT abundance stimulated at a transcriptional level, and the administration of F. nucleatum or butyrate enhanced NVDR by increasing DAT expression. The findings indicate that F. nucleatum supports AUD through epigenetic regulation of dopamine signaling and identify potential targets for AUD treatment.
期刊介绍:
"Science Signaling" is a reputable, peer-reviewed journal dedicated to the exploration of cell communication mechanisms, offering a comprehensive view of the intricate processes that govern cellular regulation. This journal, published weekly online by the American Association for the Advancement of Science (AAAS), is a go-to resource for the latest research in cell signaling and its various facets.
The journal's scope encompasses a broad range of topics, including the study of signaling networks, synthetic biology, systems biology, and the application of these findings in drug discovery. It also delves into the computational and modeling aspects of regulatory pathways, providing insights into how cells communicate and respond to their environment.
In addition to publishing full-length articles that report on groundbreaking research, "Science Signaling" also features reviews that synthesize current knowledge in the field, focus articles that highlight specific areas of interest, and editor-written highlights that draw attention to particularly significant studies. This mix of content ensures that the journal serves as a valuable resource for both researchers and professionals looking to stay abreast of the latest advancements in cell communication science.