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Medium-Dose Chronic Cannabidiol Treatment Reverses Object Recognition Memory Deficits of APP (Swe) /PS1ΔE9 Transgenic Female Mice

Alzheimer’s disease (AD) is a neurodegenerative disease that causes behavioral and cognitive impairments. The phytocannabinoid cannabidiol (CBD) has anti-inflammatory, antioxidant, and neuroprotective properties, and in vitro and limited in vivo evidence suggests that CBD possesses therapeutic-like...

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Autores principales: Coles, Madilyn, Watt, Georgia, Kreilaus, Fabian, Karl, Tim
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7789874/
https://www.ncbi.nlm.nih.gov/pubmed/33424597
http://dx.doi.org/10.3389/fphar.2020.587604
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author Coles, Madilyn
Watt, Georgia
Kreilaus, Fabian
Karl, Tim
author_facet Coles, Madilyn
Watt, Georgia
Kreilaus, Fabian
Karl, Tim
author_sort Coles, Madilyn
collection PubMed
description Alzheimer’s disease (AD) is a neurodegenerative disease that causes behavioral and cognitive impairments. The phytocannabinoid cannabidiol (CBD) has anti-inflammatory, antioxidant, and neuroprotective properties, and in vitro and limited in vivo evidence suggests that CBD possesses therapeutic-like properties for the treatment of AD. Cannabinoids are known to have dose-dependent effects and the therapeutic potential of medium-dose CBD for AD transgenic mice has not been assessed in great detail yet. 12-month-old control and APP (Swe) /PS1ΔE9 (APPxPS1) transgenic female mice were treated daily via intraperitoneal injection with 5 mg/kg bodyweight CBD (or vehicle) commencing three weeks prior to the assessment of behavioral domains including anxiety, exploration, locomotion, motor functions, cognition, and sensorimotor gating. APPxPS1 mice exhibited a hyperlocomotive and anxiogenic-like phenotype and had wild type-like motor and spatial learning abilities, although AD transgenic mice took generally longer to complete the cheeseboard training (due to a lower locomotion speed). Furthermore spatial learning and reversal learning was delayed by one day in APPxPS1 mice compared to control mice. All mice displayed intact spatial memory and retrieval memory, but APPxPS1 mice showed reduced levels of perseverance in the cheeseboard probe trial. Importantly, vehicle-treated APPxPS1 mice were characterized by object recognition deficits and delayed spatial learning, which were reversed by CBD treatment. Finally, impairments in sensorimotor gating of APPxPS1 mice were not affected by CBD. In conclusion, medium-dose CBD appears to have therapeutic value for the treatment of particular behavioral impairments present in AD patients. Future research should consider the molecular mechanisms behind CBD’s beneficial properties for AD transgenic mice.
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spelling pubmed-77898742021-01-08 Medium-Dose Chronic Cannabidiol Treatment Reverses Object Recognition Memory Deficits of APP (Swe) /PS1ΔE9 Transgenic Female Mice Coles, Madilyn Watt, Georgia Kreilaus, Fabian Karl, Tim Front Pharmacol Pharmacology Alzheimer’s disease (AD) is a neurodegenerative disease that causes behavioral and cognitive impairments. The phytocannabinoid cannabidiol (CBD) has anti-inflammatory, antioxidant, and neuroprotective properties, and in vitro and limited in vivo evidence suggests that CBD possesses therapeutic-like properties for the treatment of AD. Cannabinoids are known to have dose-dependent effects and the therapeutic potential of medium-dose CBD for AD transgenic mice has not been assessed in great detail yet. 12-month-old control and APP (Swe) /PS1ΔE9 (APPxPS1) transgenic female mice were treated daily via intraperitoneal injection with 5 mg/kg bodyweight CBD (or vehicle) commencing three weeks prior to the assessment of behavioral domains including anxiety, exploration, locomotion, motor functions, cognition, and sensorimotor gating. APPxPS1 mice exhibited a hyperlocomotive and anxiogenic-like phenotype and had wild type-like motor and spatial learning abilities, although AD transgenic mice took generally longer to complete the cheeseboard training (due to a lower locomotion speed). Furthermore spatial learning and reversal learning was delayed by one day in APPxPS1 mice compared to control mice. All mice displayed intact spatial memory and retrieval memory, but APPxPS1 mice showed reduced levels of perseverance in the cheeseboard probe trial. Importantly, vehicle-treated APPxPS1 mice were characterized by object recognition deficits and delayed spatial learning, which were reversed by CBD treatment. Finally, impairments in sensorimotor gating of APPxPS1 mice were not affected by CBD. In conclusion, medium-dose CBD appears to have therapeutic value for the treatment of particular behavioral impairments present in AD patients. Future research should consider the molecular mechanisms behind CBD’s beneficial properties for AD transgenic mice. Frontiers Media S.A. 2020-12-04 /pmc/articles/PMC7789874/ /pubmed/33424597 http://dx.doi.org/10.3389/fphar.2020.587604 Text en Copyright © 2020 Coles, Watt, Kreilaus and Karl http://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
Coles, Madilyn
Watt, Georgia
Kreilaus, Fabian
Karl, Tim
Medium-Dose Chronic Cannabidiol Treatment Reverses Object Recognition Memory Deficits of APP (Swe) /PS1ΔE9 Transgenic Female Mice
title Medium-Dose Chronic Cannabidiol Treatment Reverses Object Recognition Memory Deficits of APP (Swe) /PS1ΔE9 Transgenic Female Mice
title_full Medium-Dose Chronic Cannabidiol Treatment Reverses Object Recognition Memory Deficits of APP (Swe) /PS1ΔE9 Transgenic Female Mice
title_fullStr Medium-Dose Chronic Cannabidiol Treatment Reverses Object Recognition Memory Deficits of APP (Swe) /PS1ΔE9 Transgenic Female Mice
title_full_unstemmed Medium-Dose Chronic Cannabidiol Treatment Reverses Object Recognition Memory Deficits of APP (Swe) /PS1ΔE9 Transgenic Female Mice
title_short Medium-Dose Chronic Cannabidiol Treatment Reverses Object Recognition Memory Deficits of APP (Swe) /PS1ΔE9 Transgenic Female Mice
title_sort medium-dose chronic cannabidiol treatment reverses object recognition memory deficits of app (swe) /ps1δe9 transgenic female mice
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7789874/
https://www.ncbi.nlm.nih.gov/pubmed/33424597
http://dx.doi.org/10.3389/fphar.2020.587604
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