Largely as a consequence of changes in modern lifestyle, a significant proportion of global population have become obese. When obese people grow old, pathologies aggravate neurodegeneration. Several studies have demonstrated that both aging and obesity have deleterious impact on brain. However, the time course effects of combined aging-induced by d-galactose and obesity caused by high-fat diet on cognitive and brain function have not been explored. We hypothesize that D-galactose accelerates and aggravates brain pathologies and cognitive dysfunction in the state of obesity. Ninety-six Wistar rats were separated into two groups to be fed with either a normal diet (ND) or a high-fat diet (HFD) for 16 to 20 weeks. At the end of 12 weeks, ND and HFD-fed rats were injected with vehicle (0.9% NSS, s.c) or d-galactose (150 mg/kg/d, s.c) for 4 or 8 weeks. Data from behavioral test, metabolic parameters and brain pathologies were determined at 4 and 8-weeks after d-galactose administration. The results from both d-galactose-treated rats and HFD-fed rats showed that there was an equal increase in advanced glycation end products, and microglial activation, and an impairment in long-term depression, long-term potentiation, and synaptic protein and dendritic spine density in hippocampus, resulting in cognitive decline. However, d-galactose did not accelerate or aggravate these parameters and cognitive decline in HFD-fed rats. These results suggest that aging, obesity, and combined model have equally adverse effects on cognition. These findings can be used to increase public awareness of the negative impact of both aging and obesity on neurodegeneration.

很大程度上由于现代生活方式的改变，全球人口中很大一部分变得肥胖。当肥胖者变老时，病理加剧了神经变性。多项研究表明，衰老和肥胖对大脑都有有害影响。然而，尚未探讨由d-半乳糖引起的衰老和高脂饮食引起的肥胖对认知和脑功能的时程效应。我们假设D-半乳糖会加速并加重肥胖状态下的脑部疾病和认知功能障碍。将96只Wistar大鼠分为两组，分别接受正常饮食（ND）或高脂饮食（HFD）喂养16至20周。在第12周结束时，给ND和HFD喂养的大鼠注射媒介物（0.9％NSS，sc）或d-半乳糖（150 mg / kg / d，皮下注射）持续4或8周。d-半乳糖给药后第4周和第8周确定来自行为测试，代谢参数和脑部病理的数据。来自两个结果d半乳糖处理的大鼠和HFD喂养大鼠表明，在晚期糖化终产物等量增加，和小胶质细胞活化，并且在长期抑郁，长时程增强的损害，和突触蛋白和海马中的树突棘密度高，导致认知能力下降。但是，dβ-半乳糖不会加速或加重由HFD喂养的大鼠的这些参数和认知能力下降。这些结果表明，衰老，肥胖和综合模型对认知同样具有不利影响。这些发现可用于提高公众对衰老和肥胖对神经变性的负面影响的认识。