Xiaoyao San ameliorates maternal inflammation-induced neurobehavioral deficits by modulating the microbiota-gut-brain axis in offspring

被引:0
作者
Lin, Chunqiao [1 ,2 ]
Zhu, Jiushuang [1 ]
Zhang, Lu [1 ]
Shi, Lijie [1 ]
Zhong, Zhuoting [1 ]
Xia, Xiuwen [1 ]
Ding, Weijun [1 ]
Yang, Youjun [1 ]
机构
[1] Chengdu Univ Tradit Chinese Med, Sch Basic Med Sci, Chengdu, Peoples R China
[2] Sichuan Coll Tradit Chinese Med, Mianyang, Peoples R China
关键词
Xiaoyao san; neurodevelopmental disorders; maternal immune activation (MIA); gut microbiota; amino acid transporter; AUTISM SPECTRUM DISORDER; IMMUNE ACTIVATION; GENE-EXPRESSION; AMINO-ACIDS; MOUSE; ABNORMALITIES; REGULATORS; PREGNANCY; TRANSPORT; LEADS;
D O I
10.3389/fphar.2025.1563496
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Background XiaoYao San (XYS), a classical Traditional Chinese Medicine (TCM), has demonstrated efficacy in alleviating stress-related neuropsychiatric disorders. However, its therapeutic potential against maternal immune activation (MIA)-induced neurobehavioral impairments remains unexplored. This study aims to investigate the neuroprotective effects of XYS on MIA-related behavioral dysfunctions and elucidate its underlying mechanisms.Results Using a poly (I:C)-induced MIA mouse model, we demonstrated that XYS effectively ameliorates autism spectrum disorder (ASD) related behavioral phenotypes. Mechanistic investigations revealed that XYS exerts its therapeutic effects through: (1) Attenuation of core behavioral deficits including enhanced social interaction and reduced repetitive behaviors; (2) Downregulation of intestinal amino acid transporters; (3) Restoration of cerebral glutamate-GABA balance via modulation of glutamine pathway; (4) Structural remodeling of gut microbiota with specific enrichment of Bacteroides spp. Notably, B. uniformis was identified as a key microbial mediator capable of recapitulating XYS-mediated neurophysiological improvements through metabolic regulation.Conclusion This study elucidates XYS as a multi-target therapeutic agent that coordinately modulates gut microbial ecosystems, amino acid homeostasis, and neurotransmitter homeostasis. The findings provide novel insights into the gut-brain axis mechanisms of TCM formulations, offering a scientific foundation for developing microbiota-based intervention strategies for neurodevelopmental disorders.
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页数:18
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共 66 条
[1]   Infant microbes and metabolites point to childhood neurodevelopmental disorders [J].
Ahrens, Angelica P. ;
Hyotylainen, Tuulia ;
Petrone, Joseph R. ;
Igelstrom, Kajsa ;
George, Christian D. ;
Garrett, Timothy J. ;
Oresic, Matej ;
Triplett, Eric W. ;
Ludvigsson, Johnny .
CELL, 2024, 187 (08) :1853-1873.e15
[2]   Glutamate metabolism and recycling at the excitatory synapse in health and neurodegeneration [J].
Andersen, Jens, V ;
Markussen, Kia H. ;
Jakobsen, Emil ;
Schousboe, Arne ;
Waagepetersen, Helle S. ;
Rosenberg, Paul A. ;
Aldana, Blanca, I .
NEUROPHARMACOLOGY, 2021, 196
[3]   Deficient astrocyte metabolism impairs glutamine synthesis and neurotransmitter homeostasis in a mouse model of Alzheimer's disease [J].
Andersen, Jens, V ;
Christensen, Sofie K. ;
Westi, Emil W. ;
Diaz-delCastillo, Marta ;
Tanila, Heikki ;
Schousboe, Arne ;
Aldana, Blanca, I ;
Waagepetersen, Helle S. .
NEUROBIOLOGY OF DISEASE, 2021, 148
[4]   Marble Burying and Nestlet Shredding as Tests of Repetitive, Compulsive-like Behaviors in Mice [J].
Angoa-Perez, Mariana ;
Kane, Michael J. ;
Briggs, Denise I. ;
Francescutti, Dina M. ;
Kuhn, Donald M. .
JOVE-JOURNAL OF VISUALIZED EXPERIMENTS, 2013, (82) :50978
[5]   The glutamate/GABA-glutamine cycle: aspects of transport, neurotransmitter homeostasis and ammonia transfer [J].
Bak, Lasse K. ;
Schousboe, Arne ;
Waagepetersen, Helle S. .
JOURNAL OF NEUROCHEMISTRY, 2006, 98 (03) :641-653
[6]   Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve [J].
Bravo, Javier A. ;
Forsythe, Paul ;
Chew, Marianne V. ;
Escaravage, Emily ;
Savignac, Helene M. ;
Dinan, Timothy G. ;
Bienenstock, John ;
Cryan, John F. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2011, 108 (38) :16050-16055
[7]   Amino acids as regulators of gene expression in mammals: Molecular mechanisms [J].
Bruhat, Alain ;
Cherasse, Yoan ;
Chaveroux, Cedric ;
Maurin, Anne-Catherine ;
Jousse, Celine ;
Fafournoux, Pierre .
BIOFACTORS, 2009, 35 (03) :249-257
[8]   Microbial Reconstitution Reverses Maternal Diet-Induced Social and Synaptic Deficits in Offspring [J].
Buffington, Shelly A. ;
Di Prisco, Gonzalo Viana ;
Auchtung, Thomas A. ;
Ajami, Nadim J. ;
Petrosino, Joseph F. ;
Costa-Mattioli, Mauro .
CELL, 2016, 165 (07) :1762-1775
[9]   Maternal immune activation leads to selective functional deficits in offspring parvalbumin interneurons [J].
Canetta, S. ;
Bolkan, S. ;
Padilla-Coreano, N. ;
Song, L. J. ;
Sahn, R. ;
Harrison, N. L. ;
Gordon, J. A. ;
Brown, A. ;
Kellendonk, C. .
MOLECULAR PSYCHIATRY, 2016, 21 (07) :956-968
[10]   Maternal Immune Activation and Autism Spectrum Disorder: From Rodents to Nonhuman and Human Primates [J].
Careaga, Milo ;
Murai, Takeshi ;
Bauman, Melissa D. .
BIOLOGICAL PSYCHIATRY, 2017, 81 (05) :391-401