Kim, Juyong Choi, Pilju Park, Young-Tae Kim, Taejung Ham, Jungyeob Kim, Jin-Chul 2024-01-19T09:34:17Z 2024-01-19T09:34:17Z 2023-05-11 2023-04 1661-6596 https://pubs.kist.re.kr/handle/201004/113816 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 A beta(1-42)-treated mouse model. We observed that A beta(1-42)-treated mice had more hippocampal A beta 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 A beta and p-tau and superior cognitive function compared with A beta(1-42)-treated mice. In addition, CBDA and THCA lowered A beta 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 Ca2+, A beta, and p-tau levels. Together, CBDA and THCA may be useful therapeutic agents for treating AD. English Multidisciplinary Digital Publishing Institute (MDPI) The Cannabinoids, CBDA and THCA, Rescue Memory Deficits and Reduce Amyloid-Beta and Tau Pathology in an Alzheimer's Disease-like Mouse Model Article 10.3390/ijms24076827 1 International Journal of Molecular Sciences, v.24, no.7 International Journal of Molecular Sciences 24 7 Y scie scopus 000969780000001 2-s2.0-85152344782 Biochemistry & Molecular Biology Chemistry, Multidisciplinary Biochemistry & Molecular Biology Chemistry Article CANNABIDIOLIC ACID PROTEIN EXPRESSION CALCIUM REGULATION WATER-MAZE RECEPTORS HYPOTHESIS AGONIST INFLUX BDNF Alzheimer&apos s disease apoptosis CBDA THCA cannabinoid calcium