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Methamphetamine Induces Systemic Inflammation and Anxiety: The Role of the Gut–Immune–Brain Axis

Methamphetamine (METH) is a highly addictive drug abused by millions of users worldwide, thus becoming a global health concern with limited management options. The inefficiency of existing treatment methods has driven research into understanding the mechanisms underlying METH-induced disorders and f...

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Autores principales: Davidson, Majid, Mayer, Marina, Habib, Amanda, Rashidi, Niloufar, Filippone, Rhiannon Talia, Fraser, Sarah, Prakash, Monica D., Sinnayah, Puspha, Tangalakis, Kathy, Mathai, Michael L., Nurgali, Kulmira, Apostolopoulos, Vasso
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9569811/
https://www.ncbi.nlm.nih.gov/pubmed/36232524
http://dx.doi.org/10.3390/ijms231911224
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author Davidson, Majid
Mayer, Marina
Habib, Amanda
Rashidi, Niloufar
Filippone, Rhiannon Talia
Fraser, Sarah
Prakash, Monica D.
Sinnayah, Puspha
Tangalakis, Kathy
Mathai, Michael L.
Nurgali, Kulmira
Apostolopoulos, Vasso
author_facet Davidson, Majid
Mayer, Marina
Habib, Amanda
Rashidi, Niloufar
Filippone, Rhiannon Talia
Fraser, Sarah
Prakash, Monica D.
Sinnayah, Puspha
Tangalakis, Kathy
Mathai, Michael L.
Nurgali, Kulmira
Apostolopoulos, Vasso
author_sort Davidson, Majid
collection PubMed
description Methamphetamine (METH) is a highly addictive drug abused by millions of users worldwide, thus becoming a global health concern with limited management options. The inefficiency of existing treatment methods has driven research into understanding the mechanisms underlying METH-induced disorders and finding effective treatments. This study aims to understand the complex interactions of the gastrointestinal–immune–nervous systems following an acute METH dose administration as one of the potential underlying molecular mechanisms concentrating on the impact of METH abuse on gut permeability. Findings showed a decreased expression of tight junction proteins ZO-1 and EpCAm in intestinal tissue and the presence of FABP-1 in sera of METH treated mice suggests intestinal wall disruption. The increased presence of CD45+ immune cells in the intestinal wall further confirms gut wall inflammation/disruption. In the brain, the expression of inflammatory markers Ccl2, Cxcl1, IL-1β, TMEM119, and the presence of albumin were higher in METH mice compared to shams, suggesting METH-induced blood–brain barrier disruption. In the spleen, cellular and gene changes are also noted. In addition, mice treated with an acute dose of METH showed anxious behavior in dark and light, open field, and elevated maze tests compared to sham controls. The findings on METH-induced inflammation and anxiety may provide opportunities to develop effective treatments for METH addiction in the future.
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spelling pubmed-95698112022-10-17 Methamphetamine Induces Systemic Inflammation and Anxiety: The Role of the Gut–Immune–Brain Axis Davidson, Majid Mayer, Marina Habib, Amanda Rashidi, Niloufar Filippone, Rhiannon Talia Fraser, Sarah Prakash, Monica D. Sinnayah, Puspha Tangalakis, Kathy Mathai, Michael L. Nurgali, Kulmira Apostolopoulos, Vasso Int J Mol Sci Article Methamphetamine (METH) is a highly addictive drug abused by millions of users worldwide, thus becoming a global health concern with limited management options. The inefficiency of existing treatment methods has driven research into understanding the mechanisms underlying METH-induced disorders and finding effective treatments. This study aims to understand the complex interactions of the gastrointestinal–immune–nervous systems following an acute METH dose administration as one of the potential underlying molecular mechanisms concentrating on the impact of METH abuse on gut permeability. Findings showed a decreased expression of tight junction proteins ZO-1 and EpCAm in intestinal tissue and the presence of FABP-1 in sera of METH treated mice suggests intestinal wall disruption. The increased presence of CD45+ immune cells in the intestinal wall further confirms gut wall inflammation/disruption. In the brain, the expression of inflammatory markers Ccl2, Cxcl1, IL-1β, TMEM119, and the presence of albumin were higher in METH mice compared to shams, suggesting METH-induced blood–brain barrier disruption. In the spleen, cellular and gene changes are also noted. In addition, mice treated with an acute dose of METH showed anxious behavior in dark and light, open field, and elevated maze tests compared to sham controls. The findings on METH-induced inflammation and anxiety may provide opportunities to develop effective treatments for METH addiction in the future. MDPI 2022-09-23 /pmc/articles/PMC9569811/ /pubmed/36232524 http://dx.doi.org/10.3390/ijms231911224 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Davidson, Majid
Mayer, Marina
Habib, Amanda
Rashidi, Niloufar
Filippone, Rhiannon Talia
Fraser, Sarah
Prakash, Monica D.
Sinnayah, Puspha
Tangalakis, Kathy
Mathai, Michael L.
Nurgali, Kulmira
Apostolopoulos, Vasso
Methamphetamine Induces Systemic Inflammation and Anxiety: The Role of the Gut–Immune–Brain Axis
title Methamphetamine Induces Systemic Inflammation and Anxiety: The Role of the Gut–Immune–Brain Axis
title_full Methamphetamine Induces Systemic Inflammation and Anxiety: The Role of the Gut–Immune–Brain Axis
title_fullStr Methamphetamine Induces Systemic Inflammation and Anxiety: The Role of the Gut–Immune–Brain Axis
title_full_unstemmed Methamphetamine Induces Systemic Inflammation and Anxiety: The Role of the Gut–Immune–Brain Axis
title_short Methamphetamine Induces Systemic Inflammation and Anxiety: The Role of the Gut–Immune–Brain Axis
title_sort methamphetamine induces systemic inflammation and anxiety: the role of the gut–immune–brain axis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9569811/
https://www.ncbi.nlm.nih.gov/pubmed/36232524
http://dx.doi.org/10.3390/ijms231911224
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