合成大麻素 WIN 55,212-2 可减轻 5XFAD 阿尔茨海默小鼠的认知和运动障碍，并减少淀粉样蛋白负荷。

IF 3.3 3区心理学 Q1 BEHAVIORAL SCIENCES

Pharmacology Biochemistry and Behavior Pub Date : 2025-02-01 DOI:10.1016/j.pbb.2024.173944

Johanna E.L. Möller , Franziska W. Schmitt , Daniel Günther , Alicia Stöver , Yvonne Bouter

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引用次数: 0

摘要

背景：阿尔茨海默病（AD）以认知能力下降为特征，病理特征包括β淀粉样蛋白（Aβ）斑块和炎症。尽管最近批准了抗淀粉样蛋白抗体，但仍然需要改善疾病和易于获得的治疗方法。内源性大麻素系统是阿尔茨海默病治疗的一个有希望的靶点，因为它调节与阿尔茨海默病发病有关的各种过程。目的：本研究评估合成大麻素WIN 55,212-2对老年5XFAD小鼠AD病理和行为缺陷的影响，这是一种成熟的AD模型。方法：雄性9月龄5XFAD小鼠分别给予0.2 mg/kg WIN 55,212-2或载药液42 天。在10 个月时进行记忆、焦虑和运动测试，以确定WIN 55,212-2治疗后行为和认知的潜在变化。此外，通过免疫组织化学方法量化WIN 55,212-2长期治疗对脑组织Aβ病理和神经炎症的影响。结果：WIN 55,212-2治疗改善了5XFAD小鼠在旋转棒上的运动表现，并恢复了水迷宫中的记忆缺陷。然而，WIN 55,212-2治疗并未显著影响5XFAD小鼠的焦虑样行为。此外，长期使用WIN 55,212-2治疗可减少皮层和海马的Aβ斑块病理和星形胶质细胞增生。结论：本研究强调了WIN 55,212-2通过改善认知和运动缺陷以及减少神经病理来治疗AD的潜力。这些发现支持以大麻素为基础的治疗作为一种有希望的阿尔茨海默病治疗策略，WIN 55,212-2成为潜在的候选药物。

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The synthetic cannabinoid WIN 55,212-2 attenuates cognitive and motor deficits and reduces amyloid load in 5XFAD Alzheimer mice

Background

Alzheimer's disease (AD) is characterized by cognitive decline, with pathological features including amyloid β (Aβ) plaques and inflammation. Despite recent approvals of anti-amyloid antibodies, there remains a need for disease-modifying and easily accessible therapies. The endocannabinoid system presents a promising target for AD treatment, as it regulates various processes implicated in AD pathogenesis.

Aims

This study assesses the effects of the synthetic cannabinoid WIN 55,212-2 on AD pathology and behavior deficits in aged 5XFAD mice, a well-established AD model.

Methods

Male 9-month-old 5XFAD mice received either 0.2 mg/kg WIN 55,212-2 or a vehicle solution for 42 days. Memory, anxiety, and motor tests were conducted at 10 months to identify potential changes in behavior and cognition following WIN 55,212-2 treatment. Additionally, the effects of prolonged WIN 55,212-2 treatment on Aβ pathology and neuroinflammation in the brain were quantified immunohistochemically.

Results

Therapeutic WIN 55,212-2 treatment improved the motor performance of 5XFAD mice on the rotarod and rescued memory deficits in the water maze. However, WIN 55,212-2 treatment did not significantly affect anxiety-like behavior in 5XFAD mice. Additionally, prolonged treatment with WIN 55,212-2 reduced Aβ plaque pathology and astrogliosis in the cortex and hippocampus.

Conclusions

This study highlights the therapeutic potential of WIN 55,212-2 in AD by ameliorating cognitive and motor deficits and reducing neuropathology. These findings support a cannabinoid-based therapy as a promising strategy for AD treatment, with WIN 55,212-2 emerging as a potential candidate.

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来源期刊

Pharmacology Biochemistry and Behavior 医学-行为科学

CiteScore

6.40

自引率

2.80%

发文量

122

审稿时长

38 days

期刊介绍： Pharmacology Biochemistry & Behavior publishes original reports in the areas of pharmacology and biochemistry in which the primary emphasis and theoretical context are behavioral. Contributions may involve clinical, preclinical, or basic research. Purely biochemical or toxicology studies will not be published. Papers describing the behavioral effects of novel drugs in models of psychiatric, neurological and cognitive disorders, and central pain must include a positive control unless the paper is on a disease where such a drug is not available yet. Papers focusing on physiological processes (e.g., peripheral pain mechanisms, body temperature regulation, seizure activity) are not accepted as we would like to retain the focus of Pharmacology Biochemistry & Behavior on behavior and its interaction with the biochemistry and neurochemistry of the central nervous system. Papers describing the effects of plant materials are generally not considered, unless the active ingredients are studied, the extraction method is well described, the doses tested are known, and clear and definite experimental evidence on the mechanism of action of the active ingredients is provided.