Laboratory of Nuclear Medicine (LIM 43), Department of Radiology, Faculdade de Medicina, University of Sao Paulo, Sao Paulo 05403-911, SP, Brazil.
Laboratory of Psychiatric Neuroimaging (LIM 21), Department of Psychiatry, Faculdade de Medicina, University of Sao Paulo, Sao Paulo 05403-911, SP, Brazil.
Int J Mol Sci. 2022 Jan 19;23(3):1076. doi: 10.3390/ijms23031076.
An early and persistent sign of Alzheimer's disease (AD) is glucose hypometabolism, which can be evaluated by positron emission tomography (PET) with F-2-fluoro-2-deoxy-D-glucose ([F]FDG). Cannabidiol has demonstrated neuroprotective and anti-inflammatory properties but has not been evaluated by PET imaging in an AD model. Intracerebroventricular (icv) injection of streptozotocin (STZ) is a validated model for hypometabolism observed in AD. This proof-of-concept study evaluated the effect of cannabidiol treatment in the brain glucose metabolism of an icv-STZ AD model by PET imaging. Wistar male rats received 3 mg/kg of STZ and [F]FDG PET images were acquired before and 7 days after STZ injection. Animals were treated with intraperitoneal cannabidiol (20 mg/kg-STZ-cannabidiol) or saline (STZ-saline) for one week. Novel object recognition was performed to evaluate short-term and long-term memory. [F]FDG uptake in the whole brain was significantly lower in the STZ-saline group. Voxel-based analysis revealed a hypometabolism cluster close to the lateral ventricle, which was smaller in STZ-cannabidiol animals. The brain regions with more evident hypometabolism were the striatum, motor cortex, hippocampus, and thalamus, which was not observed in STZ-cannabidiol animals. In addition, STZ-cannabidiol animals revealed no changes in memory index. Thus, this study suggests that cannabidiol could be an early treatment for the neurodegenerative process observed in AD.
阿尔茨海默病（AD）的早期和持续迹象是葡萄糖代谢低下，可以通过正电子发射断层扫描（PET）用 F-2-氟-2-脱氧-D-葡萄糖（[F]FDG）进行评估。大麻二酚具有神经保护和抗炎特性，但尚未在 AD 模型中通过 PET 成像进行评估。侧脑室（icv）注射链脲佐菌素（STZ）是 AD 中观察到代谢低下的验证模型。这项概念验证研究通过 PET 成像评估了大麻二酚治疗对 icv-STZ AD 模型大脑葡萄糖代谢的影响。雄性 Wistar 大鼠接受 3 mg/kg 的 STZ，在 STZ 注射前和 7 天后获取 [F]FDG PET 图像。动物用腹腔内大麻二酚（20 mg/kg-STZ-大麻二酚）或生理盐水（STZ-生理盐水）治疗一周。进行新物体识别以评估短期和长期记忆。STZ-生理盐水组大脑的整体 [F]FDG 摄取显着降低。体素分析显示靠近侧脑室的代谢低下簇较小，STZ-大麻二酚动物中较小。代谢低下更明显的脑区是纹状体、运动皮层、海马体和丘脑，而在 STZ-大麻二酚动物中则没有观察到。此外，STZ-大麻二酚动物的记忆指数没有变化。因此，这项研究表明，大麻二酚可能是 AD 中观察到的神经退行性过程的早期治疗方法。
