Previous studies by ourselves and others have demonstrated that both obesity and testosterone deprivation have been related to cognitive decline. We have also shown that a prebiotic and n-acetyl cysteine (NAC) improved cognitive dysfunction in obese rats and castrated-male rats. However, the effects of NAC, a prebiotic (inulin), and a combination of the two on cognition in castrated-obese rats has never been investigated. The hypothesis was that NAC and inulin attenuated cognitive decline in castrated-obese rats by improving gut dysbiosis, and decreasing oxidative stress, glial activation and apoptosis. Male Wistar rats (n = 36) were fed with either a normal diet (ND: n = 6) or a high-fat diet (HFD: n = 30) for twenty-eight weeks. The resultant obese rats had a bilateral orchiectomy (ORX) and were randomly divided into five subgroups (n = 6/ subgroup). Each subgroup was treated with one of five therapies: a vehicle; testosterone replacement (2 mg/kg/day); NAC (100 mg/kg); inulin (10%, w/w), or a combination of the NAC and inulin for four weeks. The results demonstrated that castrated-obese rats developed gut dysbiosis, metabolic disturbance, brain pathologies, and cognitive decline. All of the pathological conditions in the brain were ameliorated to an equal extent by testosterone replacement, NAC, and inulin supplementation. Interestingly, a combination of NAC and inulin had the greatest beneficial effect on cognitive function by synergistically reducing hippocampal inflammation and ameliorating glial dysmorphology. These findings suggest that a combination of NAC and inulin may confer the greatest benefits in improving cognitive function in castrated-obese male rats.

我们自己和其他人之前的研究表明，肥胖和睾酮缺乏都与认知能力下降有关。我们还表明，益生元和 n-乙酰半胱氨酸 (NAC) 可改善肥胖大鼠和阉割雄性大鼠的认知功能障碍。然而，从未研究过 NAC、一种益生元（菊粉）以及两者的组合对去势肥胖大鼠认知的影响。假设是，NAC 和菊粉通过改善肠道生态失调、减少氧化应激、神经胶质激活和细胞凋亡来减轻去势肥胖大鼠的认知能力下降。雄性 Wistar 大鼠 ( n  = 36) 被喂食正常饮食 (ND: n  = 6) 或高脂肪饮食 (HFD: n = 30) 二十八周。由此产生的肥胖大鼠进行双侧睾丸切除术（ORX）并随机分为五个亚组（n  = 6/亚组）。每个亚组都用五种疗法中的一种进行治疗：载体；睾酮替代品 (2 毫克/公斤/天); NAC (100 毫克/公斤); 菊粉 (10%, w/w)，或 NAC 和菊粉的组合，持续 4 周。结果表明，去势肥胖大鼠出现肠道菌群失调、代谢紊乱、脑部病变和认知能力下降。通过睾酮替代、NAC 和菊粉补充，大脑中的所有病理状况都得到了同等程度的改善。有趣的是，NAC 和菊粉的组合通过协同减少海马炎症和改善神经胶质畸形，对认知功能产生最大的有益影响。这些发现表明，NAC 和菊粉的组合可能在改善去势肥胖雄性大鼠的认知功能方面带来最大益处。