Influence of Acetylcholine Esterase Inhibitors and Memantine, Clinically Approved for Alzheimer’s Dementia Treatment, on Intestinal Properties of the Mouse
Four drugs are currently approved for the treatment of Alzheimer’s disease (AD) by the FDA. Three of these drugs—donepezil, rivastigmine, and galantamine—belong to the class of acetylcholine esterase inhibitors. Memantine, a NMDA receptor antagonist, represents the fourth and a combination of donepe...
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MDPI AG
2021-01-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/3/1015 |
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| author | Vu Thu Thuy Nguyen Jason Sallbach Malena dos Santos Guilherme Kristina Endres |
| author_facet | Vu Thu Thuy Nguyen Jason Sallbach Malena dos Santos Guilherme Kristina Endres |
| author_sort | Vu Thu Thuy Nguyen |
| collection | DOAJ |
| description | Four drugs are currently approved for the treatment of Alzheimer’s disease (AD) by the FDA. Three of these drugs—donepezil, rivastigmine, and galantamine—belong to the class of acetylcholine esterase inhibitors. Memantine, a NMDA receptor antagonist, represents the fourth and a combination of donepezil and memantine the fifth treatment option. Recently, the gut and its habitants, its microbiome, came into focus of AD research and added another important factor to therapeutic considerations. While the first data provide evidence that AD patients might carry an altered microbiome, the influence of administered drugs on gut properties and commensals have been largely ignored so far. However, the occurrence of digestive side effects with these drugs and the knowledge that cholinergic transmission is crucial for several gut functions enforces the question if, and how, this medication influences the gastrointestinal system and its microbial stocking. Here, we investigated aspects such as microbial viability, colonic propulsion, and properties of enteric neurons, affected by assumed intestinal concentration of the four drugs using the mouse as a model organism. All ex vivo administered drugs revealed no direct effect on fecal bacteria viability and only a high dosage of memantine resulted in reduced biofilm formation of <i>E. coli</i>. Memantine was additionally the only compound that elevated calcium influx in enteric neurons, while all acetylcholine esterase inhibitors significantly reduced esterase activity in colonic tissue specimen and prolonged propulsion time. Both, acetylcholine esterase inhibitors and memantine, had no effect on general viability and neurite outgrowth of enteric neurons. In sum, our findings indicate that all AD symptomatic drugs have the potential to affect distinct intestinal functions and with this—directly or indirectly—microbial commensals. |
| first_indexed | 2024-03-09T04:11:54Z |
| format | Article |
| id | doaj.art-a92d2813eb694158ad69709b0da98268 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T04:11:54Z |
| publishDate | 2021-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-a92d2813eb694158ad69709b0da982682023-12-03T13:59:14ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-01-01223101510.3390/ijms22031015Influence of Acetylcholine Esterase Inhibitors and Memantine, Clinically Approved for Alzheimer’s Dementia Treatment, on Intestinal Properties of the MouseVu Thu Thuy Nguyen0Jason Sallbach1Malena dos Santos Guilherme2Kristina Endres3Department of Psychiatry and Psychotherapy, University Medical Center of the Johannes Gutenberg-University Mainz, 55131 Mainz, GermanyDepartment of Psychiatry and Psychotherapy, University Medical Center of the Johannes Gutenberg-University Mainz, 55131 Mainz, GermanyDepartment of Psychiatry and Psychotherapy, University Medical Center of the Johannes Gutenberg-University Mainz, 55131 Mainz, GermanyDepartment of Psychiatry and Psychotherapy, University Medical Center of the Johannes Gutenberg-University Mainz, 55131 Mainz, GermanyFour drugs are currently approved for the treatment of Alzheimer’s disease (AD) by the FDA. Three of these drugs—donepezil, rivastigmine, and galantamine—belong to the class of acetylcholine esterase inhibitors. Memantine, a NMDA receptor antagonist, represents the fourth and a combination of donepezil and memantine the fifth treatment option. Recently, the gut and its habitants, its microbiome, came into focus of AD research and added another important factor to therapeutic considerations. While the first data provide evidence that AD patients might carry an altered microbiome, the influence of administered drugs on gut properties and commensals have been largely ignored so far. However, the occurrence of digestive side effects with these drugs and the knowledge that cholinergic transmission is crucial for several gut functions enforces the question if, and how, this medication influences the gastrointestinal system and its microbial stocking. Here, we investigated aspects such as microbial viability, colonic propulsion, and properties of enteric neurons, affected by assumed intestinal concentration of the four drugs using the mouse as a model organism. All ex vivo administered drugs revealed no direct effect on fecal bacteria viability and only a high dosage of memantine resulted in reduced biofilm formation of <i>E. coli</i>. Memantine was additionally the only compound that elevated calcium influx in enteric neurons, while all acetylcholine esterase inhibitors significantly reduced esterase activity in colonic tissue specimen and prolonged propulsion time. Both, acetylcholine esterase inhibitors and memantine, had no effect on general viability and neurite outgrowth of enteric neurons. In sum, our findings indicate that all AD symptomatic drugs have the potential to affect distinct intestinal functions and with this—directly or indirectly—microbial commensals.https://www.mdpi.com/1422-0067/22/3/1015enteric nervous systemgut-brain-axismicrobiotaneuritesneurodegeneration |
| spellingShingle | Vu Thu Thuy Nguyen Jason Sallbach Malena dos Santos Guilherme Kristina Endres Influence of Acetylcholine Esterase Inhibitors and Memantine, Clinically Approved for Alzheimer’s Dementia Treatment, on Intestinal Properties of the Mouse International Journal of Molecular Sciences enteric nervous system gut-brain-axis microbiota neurites neurodegeneration |
| title | Influence of Acetylcholine Esterase Inhibitors and Memantine, Clinically Approved for Alzheimer’s Dementia Treatment, on Intestinal Properties of the Mouse |
| title_full | Influence of Acetylcholine Esterase Inhibitors and Memantine, Clinically Approved for Alzheimer’s Dementia Treatment, on Intestinal Properties of the Mouse |
| title_fullStr | Influence of Acetylcholine Esterase Inhibitors and Memantine, Clinically Approved for Alzheimer’s Dementia Treatment, on Intestinal Properties of the Mouse |
| title_full_unstemmed | Influence of Acetylcholine Esterase Inhibitors and Memantine, Clinically Approved for Alzheimer’s Dementia Treatment, on Intestinal Properties of the Mouse |
| title_short | Influence of Acetylcholine Esterase Inhibitors and Memantine, Clinically Approved for Alzheimer’s Dementia Treatment, on Intestinal Properties of the Mouse |
| title_sort | influence of acetylcholine esterase inhibitors and memantine clinically approved for alzheimer s dementia treatment on intestinal properties of the mouse |
| topic | enteric nervous system gut-brain-axis microbiota neurites neurodegeneration |
| url | https://www.mdpi.com/1422-0067/22/3/1015 |
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