PMID- 37956855
OWN - NLM
STAT- MEDLINE
DCOM- 20231216
LR  - 20231216
IS  - 1095-953X (Electronic)
IS  - 0969-9961 (Linking)
VI  - 189
DP  - 2023 Dec
TI  - Role of the gut-brain axis via the subdiaphragmatic vagus nerve in stress 
      resilience of 3,4-methylenedioxymethamphetamine in mice exposed to chronic 
      restrain stress.
PG  - 106348
LID - S0969-9961(23)00364-9 [pii]
LID - 10.1016/j.nbd.2023.106348 [doi]
AB  - 3,4-Methylenedioxymethamphetamine (MDMA) is the most widely used illicit 
      substance worldwide. Nevertheless, recent observational studies demonstrated that 
      lifetime MDMA use among U.S. adults was associated with a lower risk of 
      depression and suicide thoughts. We recently reported that the gut-brain axis may 
      contribute to MDMA-induced stress resilience in mice. To further explore this, we 
      investigated the effects of subdiaphragmatic vagotomy (SDV) in modulating the 
      stress resilience effects of MDMA in mice subjected to chronic restrain stress 
      (CRS). Pretreatment with MDMA (10 mg/kg/day for 14 days) blocked anhedonia-like 
      behavior and reduced expression of synaptic proteins and brain-derived 
      neurotrophic factor in the prefrontal cortex (PFC) of CRS-exposed mice. 
      Interestingly, SDV blocked the beneficial effects of MDMA on these alterations in 
      CRS-exposed mice. Analysis of gut microbiome revealed alterations in four 
      measures of alpha-diversity between the sham + MDMA + CRS group and the SDV + MDMA + 
      CRS group. Moreover, specific microbes differed between the vehicle + CRS group 
      and the MDMA + CRS group, and further differences in microbial composition were 
      observed among all four groups. Untargeted metabolomics analysis showed that SDV 
      prevented the increase in plasma levels of three compounds [lactic acid, 
      1-(2-hydroxyethyl)-2,2,6-tetramethyl-4-piperidinol, 8-acetyl-7-hydroxyvumaline] 
      observed in the sham + MDMA + CRS group. Interestingly, positive correlations 
      were found between the plasma levels of two of these compounds and the abundance 
      of several microbes across all groups. In conclusion, our data suggest that the 
      gut-brain axis via the subdiaphragmatic vagus nerve might contribute to the 
      stress resilience of MDMA.
CI  - Copyright (c) 2023 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Qu, Youge
AU  - Qu Y
AD  - Division of Clinical Neuroscience, Chiba University Center for Forensic Mental 
      Health, Chiba 260-8670, Japan.
FAU - Eguchi, Akifumi
AU  - Eguchi A
AD  - Department of Sustainable Health Science, Chiba University Center for Preventive 
      Medical Sciences, Chiba 263-8522, Japan.
FAU - Ma, Li
AU  - Ma L
AD  - Division of Clinical Neuroscience, Chiba University Center for Forensic Mental 
      Health, Chiba 260-8670, Japan.
FAU - Wan, Xiayun
AU  - Wan X
AD  - Division of Clinical Neuroscience, Chiba University Center for Forensic Mental 
      Health, Chiba 260-8670, Japan.
FAU - Mori, Chisato
AU  - Mori C
AD  - Department of Sustainable Health Science, Chiba University Center for Preventive 
      Medical Sciences, Chiba 263-8522, Japan; Department of Bioenvironmental Medicine, 
      Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
FAU - Hashimoto, Kenji
AU  - Hashimoto K
AD  - Division of Clinical Neuroscience, Chiba University Center for Forensic Mental 
      Health, Chiba 260-8670, Japan. Electronic address: hashimoto@faculty.chiba-u.jp.
LA  - eng
PT  - Journal Article
DEP - 20231111
PL  - United States
TA  - Neurobiol Dis
JT  - Neurobiology of disease
JID - 9500169
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
SB  - IM
MH  - Humans
MH  - Mice
MH  - Animals
MH  - *N-Methyl-3,4-methylenedioxyamphetamine/pharmacology
MH  - Brain-Gut Axis
MH  - *Resilience, Psychological
MH  - Prefrontal Cortex
MH  - Vagus Nerve
OTO - NOTNLM
OT  - Anhedonia
OT  - Gut microbiota
OT  - MDMA
OT  - Resilience
OT  - Stress
OT  - Susceptibility
COIS- Declaration of Competing Interest Dr. Hashimoto is the inventor of filed patent 
      applications on "The use of R-ketamine in the treatment of psychiatric diseases", 
      "(S)-norketamine and salt thereof as pharmaceutical", "R-ketamine and derivative 
      thereof as prophylactic or therapeutic agent for neurodegeneration disease or 
      recognition function disorder", "Preventive or therapeutic agent and 
      pharmaceutical composition for inflammatory diseases or bone diseases", and 
      "R-ketamine and its derivatives as a preventive or therapeutic agent for a 
      neurodevelopmental disorder" by the Chiba University. Dr. Hashimoto has also 
      received speakers' honoraria, consultant fee, or research support from Abbott, 
      Boehringer-Ingelheim, Daiichi-Sankyo, Meiji Seika Pharma, Seikagaku Corporation, 
      Dainippon-Sumitomo, Taisho, Otsuka, Murakami Farm and Perception Neuroscience. 
      Other authors declare no conflict of interest.
EDAT- 2023/11/14 00:42
MHDA- 2023/12/17 09:45
CRDT- 2023/11/13 19:15
PHST- 2023/10/24 00:00 [received]
PHST- 2023/11/08 00:00 [revised]
PHST- 2023/11/09 00:00 [accepted]
PHST- 2023/12/17 09:45 [medline]
PHST- 2023/11/14 00:42 [pubmed]
PHST- 2023/11/13 19:15 [entrez]
AID - S0969-9961(23)00364-9 [pii]
AID - 10.1016/j.nbd.2023.106348 [doi]
PST - ppublish
SO  - Neurobiol Dis. 2023 Dec;189:106348. doi: 10.1016/j.nbd.2023.106348. Epub 2023 Nov 
      11.