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iNature
Ethanol, commonly known as alcohol, is one of the common abuse substances worldwide, chronic ethanol exposure can not only cause cognitive memory impairment, but also increase the risk of anxiety, depression and other mental disorders, but the specific mechanism of action is not clear
.
In recent years, it has been suggested that the intestinal microbiota may play an important regulatory role
in the process of chronic ethanol exposure causing depressive disorders.
On October 24, 2022, the team of Zhang Guohua/Wang Xiaolong of China Medical University published the latest research results online in the journal Molecular Psychiatry (IF=13).
Gut microbiota regulates chronic ethanol exposure-induced depressive-like behavior through hippocampal NLRP3-mediated neuroinflammation This study reveals the regulatory role of gut microbiota on ethanol-induced depressive disorder, and identifies a new mechanism
by which gut microbiota regulates ethanol-induced depressive disorder through peripheral inflammation and hippocampal NLRP3 inflammasomes.
such as autism, depression, Parkinson's disease and Alzheimer's disease.
Some studies also suggest that intestinal flora may have a regulatory role in ethanol-induced mental disorders, but the specific mechanism is not well understood
.
The researchers established a chronic ethanol exposure model and added a complex probiotic preparation as a treatment factor, and found that the intake of probiotics alleviated the decline of anxiety-like and depression-like behavior and intestinal flora diversity caused by ethanol to a certain extent
.
This suggests that the gut flora is associated
with ethanol-induced psychiatric disorders.
In order to rule out the direct effect of ethanol on the central nervous system, the researchers used Fecal microbiota transplantation (FMT) to transplant the intestinal microbiota of control and ethanol-exposed mice to healthy recipient mice
.
The study found that after receiving ethanol exposed to the intestinal flora of mice, the recipient mice exhibited anxiety-like, depressive-like behavior and hippocampal neuronal damage, confirming that the intestinal microbiota has a regulatory effect
on ethanol-induced depressive disorder.
The researchers also found that after receiving the intestinal microbiota transplantation of ethanol-exposed mice, the recipient mice had activation of the hippocampal NLRP3 inflammasomes and microglia activation, accompanied by an increase
in multiple inflammatory factors/chemokines.
After the researchers used adeno-associated virus (AAV) to reduce the expression of hippocampal NLRP3, it alleviated depressive-like behavior and hippocampal nerve damage caused by chronic ethanol exposure, but had no significant effect on the change of intestinal flora and the increase of LPS and inflammatory factors in the serum, suggesting that ethanol-induced depressive disorder requires the participation of hippocampal NLRP3, and the elevated LPS and inflammatory factors in ethanol-exposed mice were peripheral sources
。 The researchers further conducted FMT experiments on the intestinal flora of AAV-transfected mice, and found that although the donor mice exposed to ethanol did not show obvious depressive-like behavior, their intestinal flora could still cause anxiety-like and depressive-like behavior, elevated serum LPS and inflammatory factors, hippocampal NLRP3 inflammasome activation, neuroinflammation and neuronal damage
in recipient mice.
This indicates that the increase of peripheral LPS and inflammatory factors, and the activation of the hippocampal NLRP3 inflammasome are caused by changes in the intestinal flora
.
Finally, the researchers analyzed the mediating role
of LPS and inflammatory factors in the abundance of different species of microbiota in the depressive behavior of mice by means of multiple causal mediation analysis.
In summary, the study revealed that the intestinal flora changes caused by chronic ethanol exposure activated the hippocampal NLRP3 inflammosomes through LPS and a variety of inflammatory factors, induced neuroinflammation and caused anxiety-like and depressive behavior, which provided an important theoretical basis
for the study of ethanol-induced mental disorders.
Professor Zhang Guohua and Associate Professor Wang Xiaolong of the School of Forensic Medicine of China Medical University are the co-corresponding authors of this paper, and Dr.
Yao Hui of the School of Forensic Medicine of China Medical University (currently working in the Department of Forensic Science, Sun Yat-sen Medical College) and Dr.
Zhang Dalin of the First Affiliated Hospital of China Medical University are co-first authors
.
China Medical University is the only one to complete
this article.
The research was supported
by the National Natural Science Foundation of China and the Natural Science Foundation of Liaoning Province.
Original link: style="margin-right: auto;margin-left: auto;outline: 0px;width: 30px;display: inline-block;">
—END—
The content is [iNature]
