1. Cannabidiol improves maternal obesity-induced behavioral, neuroinflammatory and neurochemical dysfunctions in the juvenile offspring.
- Author
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da Silva Rodrigues F, Jantsch J, de Farias Fraga G, Luiza de Camargo Milczarski V, Silva Dias V, Scheid C, de Oliveira Merib J, Giovernardi M, and Padilha Guedes R
- Subjects
- Animals, Female, Pregnancy, Rats, Male, Neuroinflammatory Diseases metabolism, Neuroinflammatory Diseases drug therapy, Social Behavior, Obesity metabolism, Endocannabinoids metabolism, Cannabidiol pharmacology, Rats, Wistar, Obesity, Maternal metabolism, Anxiety metabolism, Anxiety drug therapy, Anxiety etiology, Prenatal Exposure Delayed Effects metabolism, Prefrontal Cortex metabolism, Prefrontal Cortex drug effects, Hippocampus metabolism, Hippocampus drug effects, Behavior, Animal drug effects
- Abstract
Maternal obesity is associated with an increased risk of psychiatric disorders such as anxiety, depression, schizophrenia and autism spectrum disorder in the offspring. While numerous studies focus on preventive measures targeting the mothers, only a limited number provide practical approaches for addressing the damages once they are already established. We have recently demonstrated the interplay between maternal obesity and treatment with cannabidiol (CBD) on hypothalamic inflammation and metabolic disturbances, however, little is known about this relationship on behavioral manifestations and neurochemical imbalances in other brain regions. Therefore, here we tested whether CBD treatment could mitigate anxiety-like and social behavioral alterations, as well as neurochemical disruptions in both male and female offspring of obese dams. Female Wistar rats were fed a cafeteria diet for 12 weeks prior to mating, and during gestation and lactation. Offspring received CBD (50 mg/kg) from weaning for 3 weeks. Behavioral tests assessed anxiety-like manifestations and social behavior, while neuroinflammatory and neurochemical markers were evaluated in the prefrontal cortex (PFC) and hippocampus. CBD treatment attenuated maternal obesity-induced anxiety-like and social behavioral alterations, followed by rescuing effects on imbalanced neurotransmitter and endocannabinoid concentrations and altered expression of glial markers, CB1, oxytocin and dopamine receptors, with important differences between sexes. Overall, the findings of this study provide insight into the signaling pathways for the therapeutic benefits of CBD on neuroinflammation and neurochemical imbalances caused by perinatal maternal obesity in the PFC and the hippocampus, which translates into the behavioral manifestations, highlighting the sexual dimorphism encompassing both the transgenerational effect of obesity and the endocannabinoid system., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)
- Published
- 2024
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