Cargando…

Galantamine Slows Down Plaque Formation and Behavioral Decline in the 5XFAD Mouse Model of Alzheimer’s Disease

The plant alkaloid galantamine is an established symptomatic drug treatment for Alzheimer’s disease (AD), providing temporary cognitive and global relief in human patients. In this study, the 5X Familial Alzheimer’s Disease (5XFAD) mouse model was used to investigate the effect of chronic galantamin...

Descripción completa

Detalles Bibliográficos
Autores principales: Bhattacharya, Soumee, Haertel, Christin, Maelicke, Alfred, Montag, Dirk
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3931790/
https://www.ncbi.nlm.nih.gov/pubmed/24586789
http://dx.doi.org/10.1371/journal.pone.0089454
_version_ 1782304712959197184
author Bhattacharya, Soumee
Haertel, Christin
Maelicke, Alfred
Montag, Dirk
author_facet Bhattacharya, Soumee
Haertel, Christin
Maelicke, Alfred
Montag, Dirk
author_sort Bhattacharya, Soumee
collection PubMed
description The plant alkaloid galantamine is an established symptomatic drug treatment for Alzheimer’s disease (AD), providing temporary cognitive and global relief in human patients. In this study, the 5X Familial Alzheimer’s Disease (5XFAD) mouse model was used to investigate the effect of chronic galantamine treatment on behavior and amyloid β (Aβ) plaque deposition in the mouse brain. Quantification of plaques in untreated 5XFAD mice showed a gender specific phenotype; the plaque density increased steadily reaching saturation in males after 10 months of age, whereas in females the density further increased until after 14 months of age. Moreover, females consistently displayed a higher plaque density in comparison to males of the same age. Chronic oral treatment with galantamine resulted in improved performance in behavioral tests, such as open field and light-dark avoidance, already at mildly affected stages compared to untreated controls. Treated animals of both sexes showed significantly lower plaque density in the brain, i.e., the entorhinal cortex and hippocampus, gliosis being always positively correlated to plaque load. A high dose treatment with a daily uptake of 26 mg/kg body weight was tolerated well and produced significantly larger positive effects than a lower dose treatment (14 mg/kg body weight) in terms of plaque density and behavior. These results strongly support that galantamine, in addition to improving cognitive and behavioral symptoms in AD, may have disease-modifying and neuroprotective properties, as is indicated by delayed Aβ plaque formation and reduced gliosis.
format Online
Article
Text
id pubmed-3931790
institution National Center for Biotechnology Information
language English
publishDate 2014
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-39317902014-02-25 Galantamine Slows Down Plaque Formation and Behavioral Decline in the 5XFAD Mouse Model of Alzheimer’s Disease Bhattacharya, Soumee Haertel, Christin Maelicke, Alfred Montag, Dirk PLoS One Research Article The plant alkaloid galantamine is an established symptomatic drug treatment for Alzheimer’s disease (AD), providing temporary cognitive and global relief in human patients. In this study, the 5X Familial Alzheimer’s Disease (5XFAD) mouse model was used to investigate the effect of chronic galantamine treatment on behavior and amyloid β (Aβ) plaque deposition in the mouse brain. Quantification of plaques in untreated 5XFAD mice showed a gender specific phenotype; the plaque density increased steadily reaching saturation in males after 10 months of age, whereas in females the density further increased until after 14 months of age. Moreover, females consistently displayed a higher plaque density in comparison to males of the same age. Chronic oral treatment with galantamine resulted in improved performance in behavioral tests, such as open field and light-dark avoidance, already at mildly affected stages compared to untreated controls. Treated animals of both sexes showed significantly lower plaque density in the brain, i.e., the entorhinal cortex and hippocampus, gliosis being always positively correlated to plaque load. A high dose treatment with a daily uptake of 26 mg/kg body weight was tolerated well and produced significantly larger positive effects than a lower dose treatment (14 mg/kg body weight) in terms of plaque density and behavior. These results strongly support that galantamine, in addition to improving cognitive and behavioral symptoms in AD, may have disease-modifying and neuroprotective properties, as is indicated by delayed Aβ plaque formation and reduced gliosis. Public Library of Science 2014-02-21 /pmc/articles/PMC3931790/ /pubmed/24586789 http://dx.doi.org/10.1371/journal.pone.0089454 Text en © 2014 Bhattacharya et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Bhattacharya, Soumee
Haertel, Christin
Maelicke, Alfred
Montag, Dirk
Galantamine Slows Down Plaque Formation and Behavioral Decline in the 5XFAD Mouse Model of Alzheimer’s Disease
title Galantamine Slows Down Plaque Formation and Behavioral Decline in the 5XFAD Mouse Model of Alzheimer’s Disease
title_full Galantamine Slows Down Plaque Formation and Behavioral Decline in the 5XFAD Mouse Model of Alzheimer’s Disease
title_fullStr Galantamine Slows Down Plaque Formation and Behavioral Decline in the 5XFAD Mouse Model of Alzheimer’s Disease
title_full_unstemmed Galantamine Slows Down Plaque Formation and Behavioral Decline in the 5XFAD Mouse Model of Alzheimer’s Disease
title_short Galantamine Slows Down Plaque Formation and Behavioral Decline in the 5XFAD Mouse Model of Alzheimer’s Disease
title_sort galantamine slows down plaque formation and behavioral decline in the 5xfad mouse model of alzheimer’s disease
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3931790/
https://www.ncbi.nlm.nih.gov/pubmed/24586789
http://dx.doi.org/10.1371/journal.pone.0089454
work_keys_str_mv AT bhattacharyasoumee galantamineslowsdownplaqueformationandbehavioraldeclineinthe5xfadmousemodelofalzheimersdisease
AT haertelchristin galantamineslowsdownplaqueformationandbehavioraldeclineinthe5xfadmousemodelofalzheimersdisease
AT maelickealfred galantamineslowsdownplaqueformationandbehavioraldeclineinthe5xfadmousemodelofalzheimersdisease
AT montagdirk galantamineslowsdownplaqueformationandbehavioraldeclineinthe5xfadmousemodelofalzheimersdisease