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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| Format: | Article |
| Language: | English |
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MDPI AG
2022-09-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/19/11224 |
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| author | Majid Davidson Marina Mayer Amanda Habib Niloufar Rashidi Rhiannon Talia Filippone Sarah Fraser Monica D. Prakash Puspha Sinnayah Kathy Tangalakis Michael L. Mathai Kulmira Nurgali Vasso Apostolopoulos |
| author_facet | Majid Davidson Marina Mayer Amanda Habib Niloufar Rashidi Rhiannon Talia Filippone Sarah Fraser Monica D. Prakash Puspha Sinnayah Kathy Tangalakis Michael L. Mathai Kulmira Nurgali Vasso Apostolopoulos |
| author_sort | Majid Davidson |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-09T21:42:37Z |
| format | Article |
| id | doaj.art-dfa93f05fd664ccbac3b82595d9b4f4a |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T21:42:37Z |
| publishDate | 2022-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-dfa93f05fd664ccbac3b82595d9b4f4a2023-11-23T20:29:23ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-09-0123191122410.3390/ijms231911224Methamphetamine Induces Systemic Inflammation and Anxiety: The Role of the Gut–Immune–Brain AxisMajid Davidson0Marina Mayer1Amanda Habib2Niloufar Rashidi3Rhiannon Talia Filippone4Sarah Fraser5Monica D. Prakash6Puspha Sinnayah7Kathy Tangalakis8Michael L. Mathai9Kulmira Nurgali10Vasso Apostolopoulos11Institute for Health and Sport, Victoria University, Melbourne, VIC 3021, AustraliaDevelopmental Biology of the Immune System, Life and Medical Sciences (LIMES) Institute, University of Bonn, 53115 Bonn, GermanyInstitute for Health and Sport, Victoria University, Melbourne, VIC 3021, AustraliaInstitute for Health and Sport, Victoria University, Melbourne, VIC 3021, AustraliaInstitute for Health and Sport, Victoria University, Melbourne, VIC 3021, AustraliaInstitute for Health and Sport, Victoria University, Melbourne, VIC 3021, AustraliaSchool of Health and Biomedical Sciences, RMIT University, Melbourne, VIC 3083, AustraliaInstitute for Health and Sport, Victoria University, Melbourne, VIC 3021, AustraliaFirst Year College, Victoria University, Melbourne, VIC 3011, AustraliaInstitute for Health and Sport, Victoria University, Melbourne, VIC 3021, AustraliaInstitute for Health and Sport, Victoria University, Melbourne, VIC 3021, AustraliaInstitute for Health and Sport, Victoria University, Melbourne, VIC 3021, AustraliaMethamphetamine (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.https://www.mdpi.com/1422-0067/23/19/11224methamphetamine (METH)blood–brain barrierleaky gutinflammationanxietygut–brain axis |
| spellingShingle | Majid Davidson Marina Mayer Amanda Habib Niloufar Rashidi Rhiannon Talia Filippone Sarah Fraser Monica D. Prakash Puspha Sinnayah Kathy Tangalakis Michael L. Mathai Kulmira Nurgali Vasso Apostolopoulos Methamphetamine Induces Systemic Inflammation and Anxiety: The Role of the Gut–Immune–Brain Axis International Journal of Molecular Sciences methamphetamine (METH) blood–brain barrier leaky gut inflammation anxiety gut–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 | methamphetamine (METH) blood–brain barrier leaky gut inflammation anxiety gut–brain axis |
| url | https://www.mdpi.com/1422-0067/23/19/11224 |
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