title: Long-term cannabidiol treatment prevents the development of social recognition memory deficits in Alzheimer's disease transgenic mice.
abstract: Impairments in cognitive ability and widespread pathophysiological changes caused by neurotoxicity, neuroinflammation, oxidative damage, and altered cholesterol homeostasis are associated with Alzheimer's disease (AD). Cannabidiol (CBD) has been shown to reverse cognitive deficits of AD transgenic mice and to exert neuroprotective, anti-oxidative, and anti-inflammatory properties in vitro and in vivo. Here we evaluate the preventative properties of long-term CBD treatment in male AβPPSwe/PS1ΔE9 (AβPP × PS1) mice, a transgenic model of AD. Control and AD transgenic mice were treated orally from 2.5 months of age with CBD (20 mg/kg) daily for 8 months. Mice were then assessed in the social preference test, elevated plus maze, and fear conditioning paradigms, before cortical and hippocampal tissues were analyzed for amyloid load, oxidative damage, cholesterol, phytosterols, and inflammation. We found that AβPP × PS1 mice developed a social recognition deficit, which was prevented by CBD treatment. CBD had no impact on anxiety or associative learning. The prevention of the social recognition deficit was not associated with any changes in amyloid load or oxidative damage. However, the study revealed a subtle impact of CBD on neuroinflammation, cholesterol, and dietary phytosterol retention, which deserves further investigation. This study is the first to demonstrate CBD's ability to prevent the development of a social recognition deficit in AD transgenic mice. Our findings provide the first evidence that CBD may have potential as a preventative treatment for AD with a particular relevance for symptoms of social withdrawal and facial recognition.
authors.affiliation: Neuroscience Research Australia, Randwick, NSW, Australia School of Medical Sciences, University of New South Wales, NSW, Australia.
authors.forename: David
authors.initials: D
authors.lastname: Cheng
authors.affiliation: Illawarra Health and Medical Research Institute, University of Wollongong, NSW, Australia School of Biological Sciences, University of Wollongong, NSW, Australia.
authors.forename: Adena S
authors.initials: AS
authors.lastname: Spiro
authors.affiliation: Illawarra Health and Medical Research Institute, University of Wollongong, NSW, Australia School of Biological Sciences, University of Wollongong, NSW, Australia.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Jenner
authors.affiliation: Illawarra Health and Medical Research Institute, University of Wollongong, NSW, Australia School of Biological Sciences, University of Wollongong, NSW, Australia.
authors.forename: Brett
authors.initials: B
authors.lastname: Garner
authors.affiliation: Neuroscience Research Australia, Randwick, NSW, Australia School of Medical Sciences, University of New South Wales, NSW, Australia Schizophrenia Research Institute, Darlinghurst, NSW, Australia.
authors.forename: Tim
authors.initials: T
authors.lastname: Karl
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000503:physiopathology* / Q000523:psychology; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002185:Cannabidiol / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000187:drug effects / Q000503:physiopathology; D004195:Disease Models, Animal; D006624:Hippocampus / Q000187:drug effects / Q000503:physiopathology; D006801:Humans; D008297:Male; D008569:Memory Disorders / Q000503:physiopathology* / Q000517:prevention & control*; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation; D015213:Neuroimmunomodulation / Q000187:drug effects / Q000502:physiology; D018697:Nootropic Agents / Q000494:pharmacology*; D053764:Presenilin-1 / Q000235:genetics / Q000378:metabolism; D021641:Recognition, Psychology / Q000187:drug effects / Q000502:physiology; D012919:Social Behavior
chemical_list: C545487:APP protein, human; D016564:Amyloid beta-Protein Precursor; D018697:Nootropic Agents; C508853:PSEN1 protein, human; D053764:Presenilin-1; D002185:Cannabidiol
keywords: Alzheimer's disease; amyloid load; behavior; cannabidiol; cholesterol; neuroinflammation; oxidative stress; phytosterol; social recognition memory; transgenic $A\beta PP_{Swe}$/PS1$\Delta$E9 mice