An Ultra-Low Dose of ∆9-Tetrahydrocannabinol Alleviates Alzheimer’s Disease-Related Cognitive Impairments and Modulates TrkB Receptor Expression in a 5XFAD Mouse Model |
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Authors: | Keren Nitzan Leah Ellenbogen Ziv Bentulila Dekel David Motty Franko Emanuela P Break Michal Zoharetz Alon Shamir Yosef Sarne Ravid Doron |
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Affiliation: | 1.Department of Education and Psychology, The Open University, Ra’anana 4353701, Israel;2.Faculty of Medicine, Technion–Israel Institute of Technology, Haifa 3200003, Israel;3.Mazor Mental Health Center, Akko 2423314, Israel;4.Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel |
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Abstract: | Alzheimer’s disease (AD) is the most common form of dementia, but there is still no available treatment. Δ9-tetrahydrocannabinol (THC) is emerging as a promising therapeutic agent. Using THC in conventional high doses may have deleterious effects. Therefore, we propose to use an ultra-low dose of THC (ULD-THC). We previously published that a single injection of ULD-THC ameliorated cognitive functioning in several models of brain injuries as well as in naturally aging mice. Here, 5xFAD AD model mice received a single treatment of ULD-THC (0.002 mg/kg) after disease onset and were examined in two separate experiments for cognitive functions, neurotropic, and inflammatory factors in the hippocampus. We show that a single injection of ULD-THC alleviated cognitive impairments in 6- and 12-month-old 5xFAD mice. On the biochemical level, our results indicate an imbalance between the truncated TrkB receptor isoform and the full receptor, with AD mice showing a greater tendency to express the truncated receptor, and ULD-THC improved this imbalance. We also investigated the expression of three AD-related inflammatory markers and found an ameliorating effect of ULD-THC. The current research demonstrates for the first time the beneficial effects of a single ultra-low dose of THC in a mouse model of AD after disease onset. |
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Keywords: | Alzheimer’ s disease ultra-low dose of THC 5xFAD mice model cognition truncated TrkB receptor full TrkB receptor |
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