Abstract
An early and persistent sign of Alzheimer’s disease (AD) is glucose hypometabolism, which can be evaluated by positron emission tomography (PET) with 18F-2-fluoro-2-deoxy-D-glucose ([18F]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 [18F]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. [18F]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.
Highlights
Alzheimer’s disease (AD) has a multifactorial nature and is the most common neurodegenerative disease, being the main cause of dementia in the world [1]
Our findings showed memory deficit after STZ injection; the short- and long-term memory was preserved by the cannabidiol treatment compared to animals without treatment
Since [18F]FDG is a glucose analogue and its uptake, especially brain uptake, can be changed by the blood glucose level [14], it is important to emphasize that the animals in this study presented no alterations in this parameter, which could be explained by the STZ administration route and is in agreement with the literature [15]
Summary
Alzheimer’s disease (AD) has a multifactorial nature and is the most common neurodegenerative disease, being the main cause of dementia in the world [1]. Streptozotocin (STZ), a glucosamine– nitrosourea compound [2] derived from soil bacteria and originally developed as an anticancer agent, has been used for diabetes models in animals since 1963. In the mid-1990s, the suggestion was raised that an intracerebroventricular (icv) injection of STZ could be an option to develop an animal model for AD. Icv-STZ injection can decrease cerebral glucose uptake and produce multiple other effects that resemble the molecular, pathological, and behavioral features of the sporadic form of AD, including neuroinflammation. Sporadic AD has pathological, and behavioral features of the sporadic form of AD, including neuroinflammation. The glucose hypometabolism and desensitizing brain insulin receptors, observed in an icv-STZ model, are an early and persistent sign of sporadic AD and can be evaluated by positron emission tomography (PET) with 18F-2-fluoro-2-deoxy-D-glucose ([18F]FDG)
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