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Review
. 2022 May 10:9:783121.
doi: 10.3389/fmed.2022.783121. eCollection 2022.

Related Effects of Methamphetamine on the Intestinal Barrier via Cytokines, and Potential Mechanisms by Which Methamphetamine May Occur on the Brain-Gut Axis

Yuansen Li  1   2 , Deshenyue Kong  1   2 , Ke Bi  1   2 , Huayou Luo  1   2   3
Affiliations
Review

Related Effects of Methamphetamine on the Intestinal Barrier via Cytokines, and Potential Mechanisms by Which Methamphetamine May Occur on the Brain-Gut Axis

Yuansen Li et al. Front Med (Lausanne). .

Abstract

Methamphetamine (METH) is an illegal drug widely abused in many countries. Methamphetamine abuse is a major health and social problem all over the world. However, the effects of METH on the digestive system have rarely been reported. Previous studies and clinical cases have shown that METH use can lead to the impaired intestinal barrier function and severe digestive diseases. METH can cause multiple organ dysfunction, especially in the central nervous system (CNS). The gut microbiota are involved in the development of various CNS-related diseases via the gut-brain axis (GBA). Here, we describe the related effects of METH on the intestinal barrier via cytokines and the underlying mechanisms by which METH may occur in the brain-gut axis.

Keywords: cytokines; intestinal barrier; methamphetamine; the brain-gut axis; tight junction (TJ).

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Schematic representation of the main components of the intestinal barrier.
FIGURE 2
FIGURE 2
Intestinal barrier function was evaluated in mice and humans in the context of METH treatment. (A) Intestinal mucosal injury, intestinal wall permeability, and bacterial translocation are assessed by determining the serum levels of diamine oxidase (DAO), D-lactic acid (DLA), and endotoxin (ET) in Meth-dependent patients (MDPs). Abnormal levels of all these indicators reflect intestinal barrier dysfunction. (B) Intestinal epithelial cells of methamphetamine-treated mice are evaluated for intestinal barrier function by apoptosis, TEER, proinflammatory factors, and HE staining. Abnormal levels of all these indicators reflect intestinal barrier dysfunction.
FIGURE 3
FIGURE 3
The effects of methamphetamine on intestinal barrier function. (A) In in vitro model, methamphetamine regulates Mir-181c. Anti-mir-181c promotes the secretion of TNF-α and MLCK, resulting in increased intestinal barrier permeability (decreased tight junction related protein) and epithelial cell apoptosis. IEC-6 is a well-established rat cell line with characteristics similar to those of intestinal epithelial cells and is extensively used as a surrogate for intestinal epithelial cells, for in vitro studies. MLCK, myosin light chain kinase. (B) Self-administered methamphetamine resulted in decreased colonic barrier function [Claudin-1 and Zonula occludens-1 (ZO-1)] and impaired colonic integrity in HIV-1 transgenic rats.
FIGURE 4
FIGURE 4
Methamphetamine (METH) promotes the overexpression of NLRP3 inflammasome and induces intestinal inflammatory injury.
FIGURE 5
FIGURE 5
The effects of METH on the gut-brain axis.
See this image and copyright information in PMC

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References

    1. Davidson C, Gow AJ, Lee TH, Ellinwood EH. Methamphetamine neurotoxicity: necrotic and apoptotic mechanisms and relevance to human abuse and treatment. Brain Res Brain Res Rev. (2001) 36:1–22. 10.1016/s0165-0173(01)00054-6 - DOI - PubMed
    1. Mizoguchi H, Yamada K. Methamphetamine use causes cognitive impairment and altered decision-making. Neurochem Int. (2019) 124:106–13. 10.1016/j.neuint.2018.12.019 - DOI - PubMed
    1. Northrop NA, Yamamoto BK. Methamphetamine effects on blood-brain barrier structure and function. Front Neurosci. (2015) 9:69. 10.3389/fnins.2015.00069 - DOI - PMC - PubMed
    1. Shin EJ, Dang DK, Tran TV, Tran HQ, Jeong JH, Nah SY, et al. Current understanding of methamphetamine-associated dopaminergic neurodegeneration and psychotoxic behaviors. Arch Pharmacal Res. (2017) 40:403–28. 10.1007/s12272-017-0897-y - DOI - PubMed
    1. Frost DO, Cadet JL. Effects of methamphetamine-induced neurotoxicity on the development of neural circuitry: a hypothesis. Brain Res Brain Res Rev. (2000) 34:103–18. 10.1016/s0165-0173(00)00042-4 - DOI - PubMed

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