Medium-Dose Chronic Cannabidiol Treatment Reverses Object Recognition Memory Deficits of APPSwe/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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Frontiers Media S.A.
2020-12-01
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Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2020.587604/full |
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author | Madilyn Coles Georgia Watt Fabian Kreilaus Tim Karl Tim Karl |
author_facet | Madilyn Coles Georgia Watt Fabian Kreilaus Tim Karl Tim Karl |
author_sort | Madilyn Coles |
collection | DOAJ |
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 APPSwe/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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language | English |
last_indexed | 2024-12-14T03:10:22Z |
publishDate | 2020-12-01 |
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series | Frontiers in Pharmacology |
spelling | doaj.art-d14f1a9a4b7b452494409255110fff332022-12-21T23:19:18ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122020-12-011110.3389/fphar.2020.587604587604Medium-Dose Chronic Cannabidiol Treatment Reverses Object Recognition Memory Deficits of APPSwe/PS1ΔE9 Transgenic Female MiceMadilyn Coles0Georgia Watt1Fabian Kreilaus2Tim Karl3Tim Karl4School of Medicine, Western Sydney University, Campbelltown, NSW, AustraliaSchool of Medicine, Western Sydney University, Campbelltown, NSW, AustraliaSchool of Medicine, Western Sydney University, Campbelltown, NSW, AustraliaSchool of Medicine, Western Sydney University, Campbelltown, NSW, AustraliaNeuroscience Research Australia, Randwick, NSW, AustraliaAlzheimer’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 APPSwe/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.https://www.frontiersin.org/articles/10.3389/fphar.2020.587604/fullAlzheimer’s diseaseAPPSwe/PS1ΔE9transgenic mouse modelcannabidioltreatmentbehavior |
spellingShingle | Madilyn Coles Georgia Watt Fabian Kreilaus Tim Karl Tim Karl Medium-Dose Chronic Cannabidiol Treatment Reverses Object Recognition Memory Deficits of APPSwe/PS1ΔE9 Transgenic Female Mice Frontiers in Pharmacology Alzheimer’s disease APPSwe/PS1ΔE9 transgenic mouse model cannabidiol treatment behavior |
title | Medium-Dose Chronic Cannabidiol Treatment Reverses Object Recognition Memory Deficits of APPSwe/PS1ΔE9 Transgenic Female Mice |
title_full | Medium-Dose Chronic Cannabidiol Treatment Reverses Object Recognition Memory Deficits of APPSwe/PS1ΔE9 Transgenic Female Mice |
title_fullStr | Medium-Dose Chronic Cannabidiol Treatment Reverses Object Recognition Memory Deficits of APPSwe/PS1ΔE9 Transgenic Female Mice |
title_full_unstemmed | Medium-Dose Chronic Cannabidiol Treatment Reverses Object Recognition Memory Deficits of APPSwe/PS1ΔE9 Transgenic Female Mice |
title_short | Medium-Dose Chronic Cannabidiol Treatment Reverses Object Recognition Memory Deficits of APPSwe/PS1ΔE9 Transgenic Female Mice |
title_sort | medium dose chronic cannabidiol treatment reverses object recognition memory deficits of appswe ps1δe9 transgenic female mice |
topic | Alzheimer’s disease APPSwe/PS1ΔE9 transgenic mouse model cannabidiol treatment behavior |
url | https://www.frontiersin.org/articles/10.3389/fphar.2020.587604/full |
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