Centre for Excellence in Functional Foods, Food & Nutrition Biotechnology Division, National Agri-Food Biotechnology Institute, S.A.S Nagar, Sector 81 (Knowledge City), Punjab, India.
Centre for Excellence in Functional Foods, Food & Nutrition Biotechnology Division, National Agri-Food Biotechnology Institute, S.A.S Nagar, Sector 81 (Knowledge City), Punjab, India.
Neuropharmacology. 2024 May 15;249:109868. doi: 10.1016/j.neuropharm.2024.109868. Epub 2024 Feb 23.
Sugar bingeing induces maladaptive neuroadaptations to decrease dietary control and promote withdrawal symptoms. This study investigated sex differences in sucrose bingeing, sucrose withdrawal-induced negative mood effects and underlying neuroimmune response in the prefrontal cortex (PFC) and nucleus accumbens (NAc) of C57BL/6J male and female mice. Two-bottle sucrose choice paradigm was used to develop sucrose dependence in mice. Female mice consumed more sucrose than male mice when given free access to water and 10% sucrose for four weeks. A significant increase in the mRNA expression of neuroinflammatory markers (Il1β, Tnfα) was found in the PFC of males exposed to sucrose withdrawal. Sucrose bingeing and subsequent sucrose withdrawal showed elevated protein levels of pro-inflammatory cytokines/chemokines/growth factors in the PFC (IL-1β, IL-6, TNFα, IFN-γ, IL-10, CCL5, VEGF) and NAc (IL-1β, IL-6, IL-10, VEGF) of male mice as compared to their water controls. These effects were concurrent with reduced mRNA expression of neuronal activation marker (cFos) in the PFC of sucrose withdrawal males. One week of sucrose withdrawal after prolonged sucrose consumption showed anxiety-like behavior in male mice, not in females. In conclusion, this study demonstrates that repeated access to sucrose induces anxiety-like behavior when the sugar is no longer available in the diet and these effects are male-specific. Elevated neuroinflammation in reward neurocircuitry may underlie these sex-specific effects.
糖瘾会导致适应不良的神经适应，从而降低饮食控制能力并促进戒断症状。本研究调查了雄性和雌性 C57BL/6J 小鼠在prefrontal cortex (PFC) 和 nucleus accumbens (NAc) 中蔗糖 bingeing、蔗糖戒断引起的负面情绪效应和潜在的神经免疫反应中的性别差异。使用双瓶蔗糖选择范式在小鼠中建立蔗糖依赖。当给予雄性小鼠自由饮水和 10%蔗糖四周时，雌性小鼠消耗的蔗糖比雄性小鼠多。发现在暴露于蔗糖戒断的雄性小鼠的 PFC 中，神经炎症标志物（Il1β、Tnfα）的 mRNA 表达显著增加。蔗糖 bingeing 和随后的蔗糖戒断导致 PFC（IL-1β、IL-6、TNFα、IFN-γ、IL-10、CCL5、VEGF）和 NAc（IL-1β、IL-6、IL-10、VEGF）中促炎细胞因子/趋化因子/生长因子的蛋白水平升高与蔗糖戒断雄性小鼠 PFC 中神经元激活标记物（cFos）的 mRNA 表达降低有关。与水对照组相比，这些影响与蔗糖戒断雄性小鼠的焦虑样行为有关。在长时间摄入蔗糖后，一周的蔗糖戒断会导致雄性小鼠出现焦虑样行为，而雌性小鼠则不会。总之，本研究表明，当糖不再存在于饮食中时，反复接触蔗糖会导致焦虑样行为，而且这些影响是雄性特异性的。奖励神经回路中升高的神经炎症可能是这些性别特异性影响的基础。
