口服大麻二酚（CBD）治疗对肌萎缩性侧索硬化症（SOD1G93 A）小鼠模型的行为影响

IF 3.5 3区医学 Q2 NEUROSCIENCES

Psychopharmacology Pub Date : 2025-04-14 DOI:10.1007/s00213-025-06785-z

Sandip Ghimire, Fabian Kreilaus, Rossana Rosa Porto, Lyndsey L Anderson, Justin J Yerbury, Jonathon C Arnold, Tim Karl

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引用次数: 0

摘要

背景：肌萎缩性侧索硬化症（ALS）是一种进行性神经退行性疾病，在疾病后期影响随意肌运动以及认知和其他行为领域。目前还没有有效的治疗ALS的方法。神经炎症升高，氧化应激和内源性大麻素系统的改变在ALS中是明显的。植物大麻素大麻二酚（CBD）具有抗炎和抗氧化特性。因此，我们评估了慢性口服大麻二酚（CBD）治疗对携带G93A突变（SOD1G93A）的铜锌超氧化物歧化酶1 (SOD1) ALS小鼠模型中ALS相关行为域的补救作用。方法：从10周龄开始，雄性和雌性SOD1G93A和野生型（WT）幼崽分别饲喂对照（CHOW）或富含cbd的CHOW（相当于每天36 mg/kg的剂量）。11 - 19周每周记录体重和运动表现，12和18周记录野外行为。研究人员还对小鼠进行了脉冲前抑制（PPI）、社会行为以及与恐惧相关的记忆测试。结果：CBD治疗改善了SOD1G93A雌性小鼠的体重减轻，倾向于恢复SOD1G93A雄性小鼠的社交能力，增强了SOD1G93A雌性小鼠的社会识别记忆，并改善了高脉冲前强度下年轻SOD1G93A雌性小鼠的PPI反应。CBD对运动障碍没有影响，但逆转了12周龄雄性SOD1G93A小鼠的焦虑样表型，降低了雄性小鼠的声惊吓反应，加强了线索冻结。结论：因此，目前的治疗性口服剂量CBD延缓了雄性和雌性小鼠的疾病进展（由体重推断），并以性别特异性的方式改善SOD1G93A小鼠的特异性认知缺陷，而不改变运动表型。

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Behavioural effects of oral cannabidiol (CBD) treatment in the superoxide dismutase 1 G93 A (SOD1^{G93 A}) mouse model of amyotrophic lateral sclerosis.

Background: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease affecting voluntary muscle movement as well as cognitive and other behavioural domains at later disease stages. No effective treatment for ALS is currently available. Elevated neuroinflammation, oxidative stress and alterations to the endocannabinoid system are evident in ALS. The phytocannabinoid cannabidiol (CBD) has anti-inflammatory and anti-oxidant properties. Thus, we evaluated the remedial effects of chronic oral cannabidiol (CBD) treatment on ALS-relevant behavioural domains in the copper-zinc superoxide dismutase 1 (SOD1) mouse model of ALS that carries a G93A mutation (SOD1^G93A).

Methods: Male and female SOD1^G93A and wild type-like (WT) littermates were fed either a control (CHOW) or CBD-enriched chow diet (equivalent to a dose of 36 mg/kg per day) beginning from 10 weeks of age. Bodyweight and motor performance were recorded weekly from 11 to 19 weeks and open field behaviours at 12 and 18 weeks. Mice were also tested for prepulse inhibition (PPI), social behaviours, as well as fear-associated memory.

Results: CBD treatment ameliorated the bodyweight loss in female SOD1^G93A mice, tended to reinstate sociability in SOD1^G93A males, strengthened social recognition memory in SOD1^G93A females, and improved the PPI response in younger SOD1^G93A females at higher prepulse intensities. CBD had no effect on motor impairments but instead reversed the anxiolytic-like phenotype of 12-week-old male SOD1^G93A mice and decreased the acoustic startle response and strengthened cue freezing in male mice.

Conclusion: Thus, the current remedial oral dose of CBD delayed disease progression (inferred by bodyweight) in both male and female mice and improve specific cognitive deficits of SOD1^G93A mice in a sex specific manner without altering the motor phenotype.

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来源期刊

Psychopharmacology 医学-精神病学

CiteScore

7.10

自引率

5.90%

发文量

257

审稿时长

2-4 weeks

期刊介绍： Official Journal of the European Behavioural Pharmacology Society (EBPS) Psychopharmacology is an international journal that covers the broad topic of elucidating mechanisms by which drugs affect behavior. The scope of the journal encompasses the following fields: Human Psychopharmacology: Experimental This section includes manuscripts describing the effects of drugs on mood, behavior, cognition and physiology in humans. The journal encourages submissions that involve brain imaging, genetics, neuroendocrinology, and developmental topics. Usually manuscripts in this section describe studies conducted under controlled conditions, but occasionally descriptive or observational studies are also considered. Human Psychopharmacology: Clinical and Translational This section comprises studies addressing the broad intersection of drugs and psychiatric illness. This includes not only clinical trials and studies of drug usage and metabolism, drug surveillance, and pharmacoepidemiology, but also work utilizing the entire range of clinically relevant methodologies, including neuroimaging, pharmacogenetics, cognitive science, biomarkers, and others. Work directed toward the translation of preclinical to clinical knowledge is especially encouraged. The key feature of submissions to this section is that they involve a focus on clinical aspects. Preclinical psychopharmacology: Behavioral and Neural This section considers reports on the effects of compounds with defined chemical structures on any aspect of behavior, in particular when correlated with neurochemical effects, in species other than humans. Manuscripts containing neuroscientific techniques in combination with behavior are welcome. We encourage reports of studies that provide insight into the mechanisms of drug action, at the behavioral and molecular levels. Preclinical Psychopharmacology: Translational This section considers manuscripts that enhance the confidence in a central mechanism that could be of therapeutic value for psychiatric or neurological patients, using disease-relevant preclinical models and tests, or that report on preclinical manipulations and challenges that have the potential to be translated to the clinic. Studies aiming at the refinement of preclinical models based upon clinical findings (back-translation) will also be considered. The journal particularly encourages submissions that integrate measures of target tissue exposure, activity on the molecular target and/or modulation of the targeted biochemical pathways. Preclinical Psychopharmacology: Molecular, Genetic and Epigenetic This section focuses on the molecular and cellular actions of neuropharmacological agents / drugs, and the identification / validation of drug targets affecting the CNS in health and disease. We particularly encourage studies that provide insight into the mechanisms of drug action at the molecular level. Manuscripts containing evidence for genetic or epigenetic effects on neurochemistry or behavior are welcome.