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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...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8910894/ https://www.ncbi.nlm.nih.gov/pubmed/35269905 http://dx.doi.org/10.3390/ijms23052757 |
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author | Wang, Yanhong Hong, Yuzhu Yan, Jiyu Brown, Breanna Lin, Xiaoyang Zhang, Xiaolin Shen, Ning Li, Minghua Cai, Jianfeng Gordon, Marcia Morgan, David Zhou, Qingyu Cao, Chuanhai |
author_facet | Wang, Yanhong Hong, Yuzhu Yan, Jiyu Brown, Breanna Lin, Xiaoyang Zhang, Xiaolin Shen, Ning Li, Minghua Cai, Jianfeng Gordon, Marcia Morgan, David Zhou, Qingyu Cao, Chuanhai |
author_sort | Wang, Yanhong |
collection | PubMed |
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. |
format | Online Article Text |
id | pubmed-8910894 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-89108942022-03-11 Low-Dose Delta-9-Tetrahydrocannabinol as Beneficial Treatment for Aged APP/PS1 Mice Wang, Yanhong Hong, Yuzhu Yan, Jiyu Brown, Breanna Lin, Xiaoyang Zhang, Xiaolin Shen, Ning Li, Minghua Cai, Jianfeng Gordon, Marcia Morgan, David Zhou, Qingyu Cao, Chuanhai Int J Mol Sci Article 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. MDPI 2022-03-02 /pmc/articles/PMC8910894/ /pubmed/35269905 http://dx.doi.org/10.3390/ijms23052757 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Wang, Yanhong Hong, Yuzhu Yan, Jiyu Brown, Breanna Lin, Xiaoyang Zhang, Xiaolin Shen, Ning Li, Minghua Cai, Jianfeng Gordon, Marcia Morgan, David Zhou, Qingyu Cao, Chuanhai Low-Dose Delta-9-Tetrahydrocannabinol as Beneficial Treatment for Aged APP/PS1 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 | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8910894/ https://www.ncbi.nlm.nih.gov/pubmed/35269905 http://dx.doi.org/10.3390/ijms23052757 |
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