Article ; Online: Chronic Treatment with 50 mg/kg Cannabidiol Improves Cognition and Moderately Reduces Aβ40 Levels in 12-Month-Old Male AβPPswe/PS1ΔE9 Transgenic Mice.
Journal of Alzheimer's disease : JAD
2020 Volume 74, Issue 3, Page(s) 937–950
Abstract: Alzheimer's disease (AD) is characterized by progressive cognitive decline and pathologically by the accumulation of amyloid-β (Aβ) and tau hyperphosphorylation causing neurodegeneration and neuroinflammation. Current AD treatments do not stop or reverse ...
| Abstract | Alzheimer's disease (AD) is characterized by progressive cognitive decline and pathologically by the accumulation of amyloid-β (Aβ) and tau hyperphosphorylation causing neurodegeneration and neuroinflammation. Current AD treatments do not stop or reverse the disease progression, highlighting the need for more effective therapeutics. The phytocannabinoid cannabidiol (CBD) has demonstrated antioxidant, anti-inflammatory, and neuroprotective properties. Furthermore, chronic CBD treatment (20 mg/kg) reverses social and object recognition memory deficits in the AβPPxPS1 transgenic mouse model with only limited effects on AD-relevant brain pathology. Importantly, studies have indicated that CBD works in a dose-dependent manner. Thus, this study determined the chronic effects of 50 mg/kg CBD in male AβPPxPS1 mice. 12-month-old mice were treated with 50 mg/kg CBD or vehicle via daily intraperitoneal injections for 3 weeks prior to behavioral testing. A variety of cognitive domains including object and social recognition, spatial and fear-associated memory were evaluated. Pathological brain analyses for AD-relevant markers were conducted using ELISA and western blot. Vehicle-treated male AβPPxPS1 mice demonstrated impaired social recognition memory and reversal spatial learning. These deficits were restored after CBD treatment. Chronic CBD tended to reduce insoluble Aβ40 levels in the hippocampus of AβPPxPS1 mice but had no effect on neuroinflammation, neurodegeneration, or PPARγ markers in the cortex. This study demonstrates that therapeutic-like effects of 50 mg/kg CBD on social recognition memory and spatial learning deficits in AβPPxPS1 mice are accompanied by moderate brain region-specific reductions in insoluble Aβ40 levels. The findings emphasize the clinical relevance of CBD treatment in AD; however, the underlying mechanisms involved require further investigation. |
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| MeSH term(s) | Alzheimer Disease/drug therapy ; Alzheimer Disease/pathology ; Alzheimer Disease/psychology ; Amyloid beta-Peptides/metabolism ; Amyloid beta-Protein Precursor/antagonists & inhibitors ; Amyloid beta-Protein Precursor/genetics ; Animals ; Brain/pathology ; Cannabidiol/therapeutic use ; Cognition/drug effects ; Dose-Response Relationship, Drug ; Fear/drug effects ; Fear/psychology ; Humans ; Male ; Mice ; Mice, Inbred C3H ; Mice, Inbred C57BL ; Mice, Transgenic ; Peptide Fragments/metabolism ; Presenilin-1/antagonists & inhibitors ; Presenilin-1/genetics ; Recognition, Psychology ; Social Behavior ; Space Perception/drug effects |
| Chemical Substances | Amyloid beta-Peptides ; Amyloid beta-Protein Precursor ; Peptide Fragments ; Presenilin-1 ; amyloid beta-protein (1-40) ; Cannabidiol (19GBJ60SN5) |
| Language | English |
| Publishing date | 2020-03-12 |
| Publishing country | Netherlands |
| Document type | Journal Article ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 1440127-7 |
| ISSN | 1875-8908 ; 1387-2877 |
| ISSN (online) | 1875-8908 |
| ISSN | 1387-2877 |
| DOI | 10.3233/JAD-191242 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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