Low-Dose Delta-9-Tetrahydrocannabinol as Beneficial Treatment for Aged APP/PS1 Mice
Studies on the effective and safe therapeutic dosage of delta-9-tetrahydrocannabinol (THC) for the treatment of Alzheimer’s disease (AD) have been sparse due to the concern about THC’s psychotropic activity. The present study focused on demonstrating the beneficial effect of low-dose THC treatment i...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-03-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/5/2757 |
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| author | Yanhong Wang Yuzhu Hong Jiyu Yan Breanna Brown Xiaoyang Lin Xiaolin Zhang Ning Shen Minghua Li Jianfeng Cai Marcia Gordon David Morgan Qingyu Zhou Chuanhai Cao |
| author_facet | Yanhong Wang Yuzhu Hong Jiyu Yan Breanna Brown Xiaoyang Lin Xiaolin Zhang Ning Shen Minghua Li Jianfeng Cai Marcia Gordon David Morgan Qingyu Zhou Chuanhai Cao |
| author_sort | Yanhong Wang |
| collection | DOAJ |
| description | Studies on the effective and safe therapeutic dosage of delta-9-tetrahydrocannabinol (THC) for the treatment of Alzheimer’s disease (AD) have been sparse due to the concern about THC’s psychotropic activity. The present study focused on demonstrating the beneficial effect of low-dose THC treatment in preclinical AD models. The effect of THC on amyloid-β (Aβ) production was examined in N2a/AβPPswe cells. An in vivo study was conducted in aged APP/PS1 transgenic mice that received an intraperitoneal injection of THC at 0.02 and 0.2 mg/kg every other day for three months. The in vitro study showed that THC inhibited Aβ aggregation within a safe dose range. Results of the radial arm water maze (RAWM) test demonstrated that treatment with 0.02 and 0.2 mg/kg of THC for three months significantly improved the spatial learning performance of aged APP/PS1 mice in a dose-dependent manner. Results of protein analyses revealed that low-dose THC treatment significantly decreased the expression of Aβ oligomers, phospho-tau and total tau, and increased the expression of Aβ monomers and phospho-GSK-3β (Ser9) in the THC-treated brain tissues. In conclusion, treatment with THC at 0.2 and 0.02 mg/kg improved the spatial learning of aged APP/PS1 mice, suggesting low-dose THC is a safe and effective treatment for AD. |
| first_indexed | 2024-03-09T20:36:48Z |
| format | Article |
| id | doaj.art-47f89bcea6d44d7a8b4f90443dc71125 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T20:36:48Z |
| publishDate | 2022-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-47f89bcea6d44d7a8b4f90443dc711252023-11-23T23:09:16ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-03-01235275710.3390/ijms23052757Low-Dose Delta-9-Tetrahydrocannabinol as Beneficial Treatment for Aged APP/PS1 MiceYanhong Wang0Yuzhu Hong1Jiyu Yan2Breanna Brown3Xiaoyang Lin4Xiaolin Zhang5Ning Shen6Minghua Li7Jianfeng Cai8Marcia Gordon9David Morgan10Qingyu Zhou11Chuanhai Cao12Department of Pharmaceutical Sciences, Taneja College of Pharmacy, University of South Florida, Tampa, FL 33612, USADepartment of Pharmaceutical Sciences, Taneja College of Pharmacy, University of South Florida, Tampa, FL 33612, USADepartment of Pharmaceutical Sciences, Taneja College of Pharmacy, University of South Florida, Tampa, FL 33612, USADepartment of Pharmaceutical Sciences, Taneja College of Pharmacy, University of South Florida, Tampa, FL 33612, USADepartment of Pharmaceutical Sciences, Taneja College of Pharmacy, University of South Florida, Tampa, FL 33612, USAByrd Alzheimer’s Center and Research Institute, Morsani College of Medicine, University of South Florida, Tampa, FL 33613, USADepartment of Pharmaceutical Sciences, Taneja College of Pharmacy, University of South Florida, Tampa, FL 33612, USADepartment of Pharmaceutical Sciences, Taneja College of Pharmacy, University of South Florida, Tampa, FL 33612, USADepartment of Chemistry, College of Arts & Sciences, University of South Florida, Tampa, FL 33620, USADepartment of Translational Neuroscience, College of Medicine, Michigan State University, Grand Rapids, MI 49503, USADepartment of Translational Neuroscience, College of Medicine, Michigan State University, Grand Rapids, MI 49503, USADepartment of Pharmaceutical Sciences, Taneja College of Pharmacy, University of South Florida, Tampa, FL 33612, USADepartment of Pharmaceutical Sciences, Taneja College of Pharmacy, University of South Florida, Tampa, FL 33612, USAStudies on the effective and safe therapeutic dosage of delta-9-tetrahydrocannabinol (THC) for the treatment of Alzheimer’s disease (AD) have been sparse due to the concern about THC’s psychotropic activity. The present study focused on demonstrating the beneficial effect of low-dose THC treatment in preclinical AD models. The effect of THC on amyloid-β (Aβ) production was examined in N2a/AβPPswe cells. An in vivo study was conducted in aged APP/PS1 transgenic mice that received an intraperitoneal injection of THC at 0.02 and 0.2 mg/kg every other day for three months. The in vitro study showed that THC inhibited Aβ aggregation within a safe dose range. Results of the radial arm water maze (RAWM) test demonstrated that treatment with 0.02 and 0.2 mg/kg of THC for three months significantly improved the spatial learning performance of aged APP/PS1 mice in a dose-dependent manner. Results of protein analyses revealed that low-dose THC treatment significantly decreased the expression of Aβ oligomers, phospho-tau and total tau, and increased the expression of Aβ monomers and phospho-GSK-3β (Ser9) in the THC-treated brain tissues. In conclusion, treatment with THC at 0.2 and 0.02 mg/kg improved the spatial learning of aged APP/PS1 mice, suggesting low-dose THC is a safe and effective treatment for AD.https://www.mdpi.com/1422-0067/23/5/2757delta-9-tetrahydrocannabinolcannabidiolAlzheimer’s diseaseradial arm water maze testamyloid-βAPP/PS1 transgenic mice |
| spellingShingle | Yanhong Wang Yuzhu Hong Jiyu Yan Breanna Brown Xiaoyang Lin Xiaolin Zhang Ning Shen Minghua Li Jianfeng Cai Marcia Gordon David Morgan Qingyu Zhou Chuanhai Cao Low-Dose Delta-9-Tetrahydrocannabinol as Beneficial Treatment for Aged APP/PS1 Mice International Journal of Molecular Sciences delta-9-tetrahydrocannabinol cannabidiol Alzheimer’s disease radial arm water maze test amyloid-β APP/PS1 transgenic mice |
| title | Low-Dose Delta-9-Tetrahydrocannabinol as Beneficial Treatment for Aged APP/PS1 Mice |
| title_full | Low-Dose Delta-9-Tetrahydrocannabinol as Beneficial Treatment for Aged APP/PS1 Mice |
| title_fullStr | Low-Dose Delta-9-Tetrahydrocannabinol as Beneficial Treatment for Aged APP/PS1 Mice |
| title_full_unstemmed | Low-Dose Delta-9-Tetrahydrocannabinol as Beneficial Treatment for Aged APP/PS1 Mice |
| title_short | Low-Dose Delta-9-Tetrahydrocannabinol as Beneficial Treatment for Aged APP/PS1 Mice |
| title_sort | low dose delta 9 tetrahydrocannabinol as beneficial treatment for aged app ps1 mice |
| topic | delta-9-tetrahydrocannabinol cannabidiol Alzheimer’s disease radial arm water maze test amyloid-β APP/PS1 transgenic mice |
| url | https://www.mdpi.com/1422-0067/23/5/2757 |
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