Bitencourt Yasmin Meireles, da Silva Rodrigues Fernanda, de Farias Fraga Gabriel, Jantsch Jeferson, Wickert Fernanda, da Silva Dias Victor, de Matos Sheila Parnoff, Reiter Keli Cristine, Rizzotto Giuliano, Giovenardi Márcia, Guedes Renata Padilha
Graduate Program in Health Sciences, Federal University of Health Sciences of Porto Alegre (UFCSPA), Porto Alegre, Brazil.
Division of Molecular Metabolism, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
Metab Brain Dis. 2025 Sep 2;40(7):256. doi: 10.1007/s11011-025-01687-7.
Maternal obesity during pregnancy poses significant health risks for both mother and progeny, including long-term impacts on brain function. In previous studies, we demonstrated that cafeteria diet (CAF) consumption during gestation induces neuroinflammation and behavioral deficits in the offspring, which are reversed by cannabidiol (CBD) treatment. However, the effects of CBD on apoptosis-related pathways in this context remain unclear. Here, we investigated whether CBD treatment can modulate pro-apoptotic signaling and glial cells morphology in adult offspring of obese mothers. Wistar rats were fed a CAF for 12 weeks before mating, during pregnancy, and lactation. Offspring received oral CBD (50 mg/kg) for 3 weeks starting at postnatal day 70. In the prefrontal cortex, we assessed apoptosis-related proteins, TNFα gene expression, and astrocytes and microglia morphology. Male and female offspring of CAF-fed dams showed increased levels of BAD, which were mitigated by CBD treatment. JNK was also elevated in female offspring of obese mothers, and CBD reduced this increase. In females, CBD treatment led to a decrease in AKT concentrations. TNFα expression was elevated in the prefrontal cortex of male offspring of obese mothers. Additionally, a reduction in GFAP- and IBA-1-positive cells in the prefrontal cortex was observed in male offspring of obese dams, which was reversed by CBD. These findings suggest that maternal obesity promotes a pro-apoptotic and inflammatory brain environment, and CBD may counteract these effects via modulation of glial activity and apoptotic pathways.
孕期母亲肥胖对母亲和后代均构成重大健康风险，包括对脑功能的长期影响。在先前的研究中，我们证明孕期食用自助餐厅式饮食（CAF）会诱发后代神经炎症和行为缺陷，而大麻二酚（CBD）治疗可逆转这些影响。然而，在此背景下CBD对凋亡相关通路的影响仍不清楚。在此，我们研究了CBD治疗是否能调节肥胖母亲成年后代的促凋亡信号传导和胶质细胞形态。Wistar大鼠在交配前、孕期和哺乳期喂食CAF 12周。后代从出生后第70天开始接受口服CBD（50毫克/千克），持续3周。在额叶前皮质，我们评估了凋亡相关蛋白、TNFα基因表达以及星形胶质细胞和小胶质细胞形态。喂食CAF的母鼠的雄性和雌性后代BAD水平升高，而CBD治疗可减轻这种升高。肥胖母亲的雌性后代JNK也升高，CBD降低了这种升高。在雌性中，CBD治疗导致AKT浓度降低。肥胖母亲的雄性后代额叶前皮质中TNFα表达升高。此外，在肥胖母鼠的雄性后代中观察到额叶前皮质中GFAP和IBA - 1阳性细胞减少，而CBD可逆转这种减少。这些发现表明，母亲肥胖会促进促凋亡和炎症性脑环境，而CBD可能通过调节胶质细胞活性和凋亡通路来抵消这些影响。
