Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Nguyen, Vu Thu Thuy, Sallbach, Jason, dos Santos Guilherme, Malena, Endres, Kristina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7864027/
https://www.ncbi.nlm.nih.gov/pubmed/33498392
http://dx.doi.org/10.3390/ijms22031015
_version_ 1783647590402752512
author Nguyen, Vu Thu Thuy
Sallbach, Jason
dos Santos Guilherme, Malena
Endres, Kristina
author_facet Nguyen, Vu Thu Thuy
Sallbach, Jason
dos Santos Guilherme, Malena
Endres, Kristina
author_sort Nguyen, Vu Thu Thuy
collection PubMed
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 E. coli. 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.
format Online
Article
Text
id pubmed-7864027
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-78640272021-02-06 Influence of Acetylcholine Esterase Inhibitors and Memantine, Clinically Approved for Alzheimer’s Dementia Treatment, on Intestinal Properties of the Mouse Nguyen, Vu Thu Thuy Sallbach, Jason dos Santos Guilherme, Malena Endres, Kristina Int J Mol Sci Article 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 E. coli. 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. MDPI 2021-01-20 /pmc/articles/PMC7864027/ /pubmed/33498392 http://dx.doi.org/10.3390/ijms22031015 Text en © 2021 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Nguyen, Vu Thu Thuy
Sallbach, Jason
dos Santos Guilherme, Malena
Endres, Kristina
Influence of Acetylcholine Esterase Inhibitors and Memantine, Clinically Approved for Alzheimer’s Dementia Treatment, on Intestinal Properties of the Mouse
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 Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7864027/
https://www.ncbi.nlm.nih.gov/pubmed/33498392
http://dx.doi.org/10.3390/ijms22031015
work_keys_str_mv AT nguyenvuthuthuy influenceofacetylcholineesteraseinhibitorsandmemantineclinicallyapprovedforalzheimersdementiatreatmentonintestinalpropertiesofthemouse
AT sallbachjason influenceofacetylcholineesteraseinhibitorsandmemantineclinicallyapprovedforalzheimersdementiatreatmentonintestinalpropertiesofthemouse
AT dossantosguilhermemalena influenceofacetylcholineesteraseinhibitorsandmemantineclinicallyapprovedforalzheimersdementiatreatmentonintestinalpropertiesofthemouse
AT endreskristina influenceofacetylcholineesteraseinhibitorsandmemantineclinicallyapprovedforalzheimersdementiatreatmentonintestinalpropertiesofthemouse