Medium-Dose Chronic Cannabidiol Treatment Reverses Object Recognition Memory Deficits of APP (Swe) /PS1ΔE9 Transgenic Female Mice.
Medium-Dose Chronic Cannabidiol Treatment Reverses Object Recognition Memory Deficits of APP (Swe) /PS1ΔE9 Transgenic Female Mice.
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中等剂量大麻二酚治疗逆转APP（Swe）/PS1ΔE9转基因雌性小鼠的物体识别记忆缺陷
DOI：
10.3389/fphar.2020.587604
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发表时间：
2020
影响因子：
5.6
通讯作者：
Karl T
中科院分区：
文献类型：
--
作者：
Coles M;Watt G;Kreilaus F;Karl T
阿尔茨海默病（AD）是一种神经退行性疾病，其导致行为和认知障碍。植物大麻素大麻二酚（CBD）具有抗炎，抗氧化和神经保护特性，体外和有限的体内证据表明，CBD具有治疗AD的治疗性质。已知大麻素具有剂量依赖性作用，并且尚未详细评估中等剂量CBD对AD转基因小鼠的治疗潜力。12月龄的对照和APP Swe /PS1ΔE9（APPxPS 1）转基因雌性小鼠在评估行为领域（包括焦虑、探索、运动、运动功能、认知和感觉运动门控）之前三周开始每天通过腹膜内注射5 mg/kg体重CBD（或媒介物）进行处理。APPxPS 1小鼠表现出超运动和焦虑样表型，并具有野生型样运动和空间学习能力，尽管AD转基因小鼠通常需要更长的时间才能完成奶酪板训练（由于运动速度较低）。此外，与对照小鼠相比，APPxPS 1小鼠的空间学习和逆转学习延迟了一天。所有小鼠都显示出完整的空间记忆和检索记忆，但APPxPS 1小鼠在奶酪板探针试验中表现出毅力水平降低。重要的是，媒介物处理的APPxPS 1小鼠的特征在于物体识别缺陷和延迟的空间学习，这被CBD处理逆转。最后，APPxPS 1小鼠的感觉运动门控损伤不受CBD的影响。总之，中等剂量CBD似乎对治疗AD患者中存在的特定行为障碍具有治疗价值。未来的研究应该考虑CBD对AD转基因小鼠有益特性背后的分子机制。
Alzheimer’s disease (AD) is a neurodegenerative disease that causes behavioral and cognitive impairments. The phytocannabinoid cannabidiol (CBD) has anti-inflammatory, antioxidant, and neuroprotective properties, and in vitro and limited in vivo evidence suggests that CBD possesses therapeutic-like properties for the treatment of AD. Cannabinoids are known to have dose-dependent effects and the therapeutic potential of medium-dose CBD for AD transgenic mice has not been assessed in great detail yet. 12-month-old control and APP Swe /PS1ΔE9 (APPxPS1) transgenic female mice were treated daily via intraperitoneal injection with 5 mg/kg bodyweight CBD (or vehicle) commencing three weeks prior to the assessment of behavioral domains including anxiety, exploration, locomotion, motor functions, cognition, and sensorimotor gating. APPxPS1 mice exhibited a hyperlocomotive and anxiogenic-like phenotype and had wild type-like motor and spatial learning abilities, although AD transgenic mice took generally longer to complete the cheeseboard training (due to a lower locomotion speed). Furthermore spatial learning and reversal learning was delayed by one day in APPxPS1 mice compared to control mice. All mice displayed intact spatial memory and retrieval memory, but APPxPS1 mice showed reduced levels of perseverance in the cheeseboard probe trial. Importantly, vehicle-treated APPxPS1 mice were characterized by object recognition deficits and delayed spatial learning, which were reversed by CBD treatment. Finally, impairments in sensorimotor gating of APPxPS1 mice were not affected by CBD. In conclusion, medium-dose CBD appears to have therapeutic value for the treatment of particular behavioral impairments present in AD patients. Future research should consider the molecular mechanisms behind CBD’s beneficial properties for AD transgenic mice.
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DOI：
10.1007/bf00421075
发表时间：
1975-01-01
期刊：
PSYCHOPHARMACOLOGIA
影响因子：
--
作者：
HAM, MT;DEJONG, Y
通讯作者：
DEJONG, Y
影响因子：
4.3
作者：
Buchman AS;Bennett DA
通讯作者：
Bennett DA
影响因子：
3.7
作者：
Esposito G;Scuderi C;Valenza M;Togna GI;Latina V;De Filippis D;Cipriano M;Carratù MR;Iuvone T;Steardo L
通讯作者：
Steardo L
影响因子：
6.7
作者：
BURNS, A;JACOBY, R;LEVY, R
通讯作者：
LEVY, R
影响因子：
6.1
作者：
Garcia-Alloza, Monica;Robbins, Elissa M.;Frosch, Matthew P.
通讯作者：
Frosch, Matthew P.