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.
摘要：
母亲肥胖与焦虑等精神疾病的风险增加有关，抑郁症,后代的精神分裂症和自闭症谱系障碍。虽然许多研究都集中在针对母亲的预防措施上，一旦损害赔偿已经确定，只有有限的数量提供了解决损害赔偿的实用方法。我们最近证明了母亲肥胖与大麻二酚（CBD）对下丘脑炎症和代谢紊乱的治疗之间的相互作用，然而,人们对这种行为表现和其他大脑区域神经化学失衡的关系知之甚少。因此,在这里，我们测试了CBD治疗是否可以减轻焦虑和社交行为改变，以及肥胖水坝的雄性和雌性后代的神经化学破坏。雌性Wistar大鼠在交配前喂食自助餐12周，在妊娠和哺乳期间。后代从断奶开始接受CBD（50mg/kg），持续3周。行为测试评估焦虑样表现和社会行为，而在前额叶皮质（PFC）和海马中评估了神经炎症和神经化学标志物。CBD治疗减轻了母亲肥胖引起的焦虑样和社会行为改变，其次是对不平衡的神经递质和内源性大麻素浓度的挽救作用以及神经胶质标志物表达的改变，CB1，催产素和多巴胺受体，性别差异很大.总的来说,这项研究的发现为CBD对PFC和海马中围产期母体肥胖引起的神经炎症和神经化学失衡的治疗益处的信号通路提供了见解，转化为行为表现，强调性二态性，包括肥胖和内源性大麻素系统的跨代效应。
