Cannabidiol Treatment Improves Glucose Metabolism and Memory in Streptozotocin-Induced Alzheimer's Disease Rat Model: A Proof-of-Concept Study

• Published in: International journal of molecular sciences 2022-01, Vol.23 (3), p.1076
• Main Authors: de Paula Faria, Daniele, Estessi de Souza, Larissa, Duran, Fabio Luis de Souza, Buchpiguel, Carlos Alberto, Britto, Luiz Roberto, Crippa, José Alexandre de Souza, Filho, Geraldo Busatto, Real, Caroline Cristiano
• Format: Article
• Language: English
• Subjects: Alzheimer Disease - chemically induced; Alzheimer Disease - diagnostic imaging; Alzheimer Disease - drug therapy; Alzheimer Disease - psychology; Alzheimer's disease; Animal cognition; Animal models; Animals; Anti-inflammatory agents; Brain - diagnostic imaging; Brain - metabolism; Cannabidiol; Cannabidiol - administration & dosage; Cannabidiol - pharmacology; Cannabinoids; Cognitive ability; Diabetes; Disease Models, Animal; Emission analysis; Fluorine isotopes; Fluorodeoxyglucose F18 - administration & dosage; Glucose; Glucose - metabolism; Hypometabolism; Image acquisition; Inflammation; Injection; Injections, Intraperitoneal; Long term memory; Male; Medical imaging; Memory; Memory, Long-Term - drug effects; Memory, Short-Term - drug effects; Metabolism; Neostriatum; Neurodegeneration; Neuroimaging; Neuroprotection; Pattern recognition; Positron emission; Positron emission tomography; Proof of Concept Study; Protein expression; Proteins; Rats; Rats, Wistar; Streptozocin; Streptozocin - adverse effects; Thalamus; Tomography; Ventricle; Ventricles (cerebral)
• ISSN: 1422-0067; 1661-6596; 1422-0067
• 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.