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Effect of long-term cannabidiol on learning and anxiety in a female Alzheimer’s disease mouse model

Cannabidiol is a promising potential therapeutic for neurodegenerative diseases, including Alzheimer’s disease (AD). Our laboratory has shown that oral CBD treatment prevents cognitive impairment in a male genetic mouse model of AD, the amyloid precursor protein 1 x presenilin 1 hemizygous (APPxPS1)...

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Autores principales: Chesworth, Rose, Cheng, David, Staub, Chloe, Karl, Tim
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9551202/
https://www.ncbi.nlm.nih.gov/pubmed/36238565
http://dx.doi.org/10.3389/fphar.2022.931384
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author Chesworth, Rose
Cheng, David
Staub, Chloe
Karl, Tim
author_facet Chesworth, Rose
Cheng, David
Staub, Chloe
Karl, Tim
author_sort Chesworth, Rose
collection PubMed
description Cannabidiol is a promising potential therapeutic for neurodegenerative diseases, including Alzheimer’s disease (AD). Our laboratory has shown that oral CBD treatment prevents cognitive impairment in a male genetic mouse model of AD, the amyloid precursor protein 1 x presenilin 1 hemizygous (APPxPS1) mouse. However, as sex differences are evident in clinical populations and in AD mouse models, we tested the preventive potential of CBD therapy in female APPxPS1 mice. In this study, 2.5-month-old female wildtype-like (WT) and APPxPS1 mice were fed 20 mg/kg CBD or a vehicle via gel pellets daily for 8 months and tested at 10.5 months in behavioural paradigms relevant to cognition (fear conditioning, FC; cheeseboard, CB; and novel object recognition test, NORT) and anxiety-like behaviours (elevated plus maze, EPM). In the CB, CBD reduced latencies to find a food reward in APPxPS1 mice, compared to vehicle-treated APPxPS1 controls, and this treatment effect was not evident in WT mice. In addition, CBD also increased speed early in the acquisition of the CB task in APPxPS1 mice. In the EPM, CBD increased locomotion in APPxPS1 mice but not in WT mice, with no effects of CBD on anxiety-like behaviour. CBD had limited effects on the expression of fear memory. These results indicate preventive CBD treatment can have a moderate spatial learning-enhancing effect in a female amyloid-β-based AD mouse model. This suggests CBD may have some preventive therapeutic potential in female familial AD patients.
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spelling pubmed-95512022022-10-12 Effect of long-term cannabidiol on learning and anxiety in a female Alzheimer’s disease mouse model Chesworth, Rose Cheng, David Staub, Chloe Karl, Tim Front Pharmacol Pharmacology Cannabidiol is a promising potential therapeutic for neurodegenerative diseases, including Alzheimer’s disease (AD). Our laboratory has shown that oral CBD treatment prevents cognitive impairment in a male genetic mouse model of AD, the amyloid precursor protein 1 x presenilin 1 hemizygous (APPxPS1) mouse. However, as sex differences are evident in clinical populations and in AD mouse models, we tested the preventive potential of CBD therapy in female APPxPS1 mice. In this study, 2.5-month-old female wildtype-like (WT) and APPxPS1 mice were fed 20 mg/kg CBD or a vehicle via gel pellets daily for 8 months and tested at 10.5 months in behavioural paradigms relevant to cognition (fear conditioning, FC; cheeseboard, CB; and novel object recognition test, NORT) and anxiety-like behaviours (elevated plus maze, EPM). In the CB, CBD reduced latencies to find a food reward in APPxPS1 mice, compared to vehicle-treated APPxPS1 controls, and this treatment effect was not evident in WT mice. In addition, CBD also increased speed early in the acquisition of the CB task in APPxPS1 mice. In the EPM, CBD increased locomotion in APPxPS1 mice but not in WT mice, with no effects of CBD on anxiety-like behaviour. CBD had limited effects on the expression of fear memory. These results indicate preventive CBD treatment can have a moderate spatial learning-enhancing effect in a female amyloid-β-based AD mouse model. This suggests CBD may have some preventive therapeutic potential in female familial AD patients. Frontiers Media S.A. 2022-09-27 /pmc/articles/PMC9551202/ /pubmed/36238565 http://dx.doi.org/10.3389/fphar.2022.931384 Text en Copyright © 2022 Chesworth, Cheng, Staub and Karl. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Chesworth, Rose
Cheng, David
Staub, Chloe
Karl, Tim
Effect of long-term cannabidiol on learning and anxiety in a female Alzheimer’s disease mouse model
title Effect of long-term cannabidiol on learning and anxiety in a female Alzheimer’s disease mouse model
title_full Effect of long-term cannabidiol on learning and anxiety in a female Alzheimer’s disease mouse model
title_fullStr Effect of long-term cannabidiol on learning and anxiety in a female Alzheimer’s disease mouse model
title_full_unstemmed Effect of long-term cannabidiol on learning and anxiety in a female Alzheimer’s disease mouse model
title_short Effect of long-term cannabidiol on learning and anxiety in a female Alzheimer’s disease mouse model
title_sort effect of long-term cannabidiol on learning and anxiety in a female alzheimer’s disease mouse model
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9551202/
https://www.ncbi.nlm.nih.gov/pubmed/36238565
http://dx.doi.org/10.3389/fphar.2022.931384
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