1 Department of Biotechnology and Life Sciences (DBSV), University of Insubria, Varese, Italy.
2 Institute of Biomolecular Chemistry, Consiglio Nazionale delle Ricerche, Pozzuoli, Naples, Italy.
J Psychopharmacol. 2019 Jul;33(7):894-907. doi: 10.1177/0269881119844184. Epub 2019 May 14.
Recent evidence suggests that 2-week treatment with the non-psychotomimetic cannabinoid cannabidivarin (CBDV) could be beneficial towards neurological and social deficits in early symptomatic mutant mice, a model of Rett syndrome (RTT).
The aim of this study was to provide further insights into the efficacy of CBDV in -null mice using a lifelong treatment schedule (from 4 to 9 weeks of age) to evaluate its effect on recognition memory and neurological defects in both early and advanced stages of the phenotype progression.
CBDV 0.2, 2, 20 and 200 mg/kg/day was administered to -null mice from 4 to 9 weeks of age. Cognitive and neurological defects were monitored during the whole treatment schedule. Biochemical analyses were carried out in brain lysates from 9-week-old wild-type and knockout mice to evaluate brain-derived neurotrophic factor (BDNF) and insulin-like growth factor-1 (IGF-1) levels as well as components of the endocannabinoid system.
CBDV rescues recognition memory deficits in mutant mice and delays the appearance of neurological defects. At the biochemical level, it normalizes BDNF/IGF1 levels and the defective PI3K/AKT/mTOR pathway in mutant mice at an advanced stage of the disease. deletion upregulates CB1 and CB2 receptor levels in the brain and these changes are restored after CBDV treatment.
CBDV administration exerts an enduring rescue of memory deficits in mutant mice, an effect that is associated with the normalization of BDNF, IGF-1 and rpS6 phosphorylation levels as well as CB1 and CB2 receptor expression. CBDV delays neurological defects but this effect is only transient.
最近的证据表明，2 周的非致幻大麻素大麻二酚（CBDV）治疗可能对早期症状突变小鼠（雷特综合征模型）的神经和社交缺陷有益。
本研究旨在通过终生治疗方案（4 至 9 周龄）进一步了解 CBDV 在 -null 小鼠中的疗效，以评估其对认知记忆和神经缺陷的影响，以及表型进展的早期和晚期阶段。
从 4 至 9 周龄开始，将 CBDV 0.2、2、20 和 200mg/kg/天给予 -null 小鼠。在整个治疗过程中监测认知和神经缺陷。在 9 周龄野生型和敲除小鼠的脑匀浆中进行生化分析，以评估脑源性神经营养因子（BDNF）和胰岛素样生长因子-1（IGF-1）水平以及内源性大麻素系统的组成部分。
CBDV 可挽救突变小鼠的识别记忆缺陷，并延迟神经缺陷的出现。在生化水平上，它可使 BDNF/IGF1 水平和疾病晚期的缺陷 PI3K/AKT/mTOR 途径正常化。在大脑中， -null 小鼠的 CB1 和 CB2 受体水平上调，这些变化在 CBDV 治疗后得到恢复。
CBDV 给药可持久挽救突变小鼠的记忆缺陷，这种作用与 BDNF、IGF-1 和 rpS6 磷酸化水平以及 CB1 和 CB2 受体表达的正常化有关。CBDV 可延迟神经缺陷，但这种作用只是暂时的。
