The Cannabinoids, CBDA and THCA, Rescue Memory Deficits and Reduce Amyloid-Beta and Tau Pathology in an Alzheimer’s Disease-like Mouse Model
Most studies related to hemp are focused on Cannabidiol (CBD) and Tetrahydrocannabinol (THC); however, up to 120 types of phytocannabinoids are present in hemp. Hemp leaves contain large amounts of Cannabidiolic acid (CBDA) and Tetrahydrocannabinolic acid (THCA), which are acidic variants of CBD and...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-04-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/7/6827 |
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| author | Juyong Kim Pilju Choi Young-Tae Park Taejung Kim Jungyeob Ham Jin-Chul Kim |
| author_facet | Juyong Kim Pilju Choi Young-Tae Park Taejung Kim Jungyeob Ham Jin-Chul Kim |
| author_sort | Juyong Kim |
| collection | DOAJ |
| description | Most studies related to hemp are focused on Cannabidiol (CBD) and Tetrahydrocannabinol (THC); however, up to 120 types of phytocannabinoids are present in hemp. Hemp leaves contain large amounts of Cannabidiolic acid (CBDA) and Tetrahydrocannabinolic acid (THCA), which are acidic variants of CBD and THC and account for the largest proportion of CBDA. In recent studies, CBDA exhibited anti-hyperalgesia and anti-inflammatory effects. THCA also showed anti-inflammatory and neuroprotective effects that may be beneficial for treating neurodegenerative diseases. CBDA and THCA can penetrate the blood–brain barrier (BBB) and affect the central nervous system. The purpose of this study was to determine whether CBDA and THCA ameliorate Alzheimer’s disease (AD)-like features in vitro and in vivo. The effect of CBDA and THCA was evaluated in the Aβ<sub>1–42</sub>-treated mouse model. We observed that Aβ<sub>1–42</sub>-treated mice had more hippocampal Aβ and p-tau levels, pathological markers of AD, and loss of cognitive function compared with PBS-treated mice. However, CBDA- and THCA-treated mice showed decreased hippocampal Aβ and p-tau and superior cognitive function compared with Aβ<sub>1–42</sub>-treated mice. In addition, CBDA and THCA lowered Aβ and p-tau levels, alleviated calcium dyshomeostasis, and exhibited neuroprotective effects in primary neurons. Our results suggest that CBDA and THCA have anti-AD effects and mitigate memory loss and resilience to increased hippocampal Ca<sup>2+</sup>, Aβ, and p-tau levels. Together, CBDA and THCA may be useful therapeutic agents for treating AD. |
| first_indexed | 2024-03-11T05:33:48Z |
| format | Article |
| id | doaj.art-6a45b8287db84559b5b2ebf48d5e0862 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T05:33:48Z |
| publishDate | 2023-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-6a45b8287db84559b5b2ebf48d5e08622023-11-17T16:56:35ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-04-01247682710.3390/ijms24076827The Cannabinoids, CBDA and THCA, Rescue Memory Deficits and Reduce Amyloid-Beta and Tau Pathology in an Alzheimer’s Disease-like Mouse ModelJuyong Kim0Pilju Choi1Young-Tae Park2Taejung Kim3Jungyeob Ham4Jin-Chul Kim5Department of Agricultural Biotechnology, Seoul National University, Seoul 08826, Republic of KoreaNatural Product Research Center, Korea Institute of Science and Technology (KIST), Gangneung 25451, Republic of KoreaNatural Product Research Center, Korea Institute of Science and Technology (KIST), Gangneung 25451, Republic of KoreaNatural Product Research Center, Korea Institute of Science and Technology (KIST), Gangneung 25451, Republic of KoreaNatural Product Research Center, Korea Institute of Science and Technology (KIST), Gangneung 25451, Republic of KoreaNatural Product Research Center, Korea Institute of Science and Technology (KIST), Gangneung 25451, Republic of KoreaMost studies related to hemp are focused on Cannabidiol (CBD) and Tetrahydrocannabinol (THC); however, up to 120 types of phytocannabinoids are present in hemp. Hemp leaves contain large amounts of Cannabidiolic acid (CBDA) and Tetrahydrocannabinolic acid (THCA), which are acidic variants of CBD and THC and account for the largest proportion of CBDA. In recent studies, CBDA exhibited anti-hyperalgesia and anti-inflammatory effects. THCA also showed anti-inflammatory and neuroprotective effects that may be beneficial for treating neurodegenerative diseases. CBDA and THCA can penetrate the blood–brain barrier (BBB) and affect the central nervous system. The purpose of this study was to determine whether CBDA and THCA ameliorate Alzheimer’s disease (AD)-like features in vitro and in vivo. The effect of CBDA and THCA was evaluated in the Aβ<sub>1–42</sub>-treated mouse model. We observed that Aβ<sub>1–42</sub>-treated mice had more hippocampal Aβ and p-tau levels, pathological markers of AD, and loss of cognitive function compared with PBS-treated mice. However, CBDA- and THCA-treated mice showed decreased hippocampal Aβ and p-tau and superior cognitive function compared with Aβ<sub>1–42</sub>-treated mice. In addition, CBDA and THCA lowered Aβ and p-tau levels, alleviated calcium dyshomeostasis, and exhibited neuroprotective effects in primary neurons. Our results suggest that CBDA and THCA have anti-AD effects and mitigate memory loss and resilience to increased hippocampal Ca<sup>2+</sup>, Aβ, and p-tau levels. Together, CBDA and THCA may be useful therapeutic agents for treating AD.https://www.mdpi.com/1422-0067/24/7/6827Alzheimer’s diseaseapoptosisCBDATHCAcannabinoidcalcium |
| spellingShingle | Juyong Kim Pilju Choi Young-Tae Park Taejung Kim Jungyeob Ham Jin-Chul Kim The Cannabinoids, CBDA and THCA, Rescue Memory Deficits and Reduce Amyloid-Beta and Tau Pathology in an Alzheimer’s Disease-like Mouse Model International Journal of Molecular Sciences Alzheimer’s disease apoptosis CBDA THCA cannabinoid calcium |
| title | The Cannabinoids, CBDA and THCA, Rescue Memory Deficits and Reduce Amyloid-Beta and Tau Pathology in an Alzheimer’s Disease-like Mouse Model |
| title_full | The Cannabinoids, CBDA and THCA, Rescue Memory Deficits and Reduce Amyloid-Beta and Tau Pathology in an Alzheimer’s Disease-like Mouse Model |
| title_fullStr | The Cannabinoids, CBDA and THCA, Rescue Memory Deficits and Reduce Amyloid-Beta and Tau Pathology in an Alzheimer’s Disease-like Mouse Model |
| title_full_unstemmed | The Cannabinoids, CBDA and THCA, Rescue Memory Deficits and Reduce Amyloid-Beta and Tau Pathology in an Alzheimer’s Disease-like Mouse Model |
| title_short | The Cannabinoids, CBDA and THCA, Rescue Memory Deficits and Reduce Amyloid-Beta and Tau Pathology in an Alzheimer’s Disease-like Mouse Model |
| title_sort | cannabinoids cbda and thca rescue memory deficits and reduce amyloid beta and tau pathology in an alzheimer s disease like mouse model |
| topic | Alzheimer’s disease apoptosis CBDA THCA cannabinoid calcium |
| url | https://www.mdpi.com/1422-0067/24/7/6827 |
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