The consumption of a processed foods diet (PD) enriched with refined carbohydrates, saturated fats, and lack of fiber has increased in recent decades and likely contributed to increased incidence of chronic disease and weight gain in humans. These diets have also been shown to negatively impact brain health and cognitive function in rodents, non-human primates, and humans, potentially through neuroimmune-related mechanisms. However, mechanisms by which PD impacts the aged brain are unknown. This gap in knowledge is critical, considering the aged brain has a heightened state of baseline inflammation, making it more susceptible to secondary challenges. Here, we showed that consumption of a PD, enriched with refined carbohydrate sources, for 28 days impaired hippocampal- and amygdalar-dependent memory function in aged (24 months), but not young (3 months) F344 × BN rats. These memory deficits were accompanied by increased expression of inflammatory genes, such as IL-1β, CD11b, MHC class II, CD86, NLRP3, and complement component 3, in the hippocampus and amygdala of aged rats. Importantly, we also showed that when the same PD is supplemented with the omega-3 polyunsaturated fatty acid DHA, these memory deficits and inflammatory gene expression changes were ameliorated in aged rats, thus providing the first evidence that DHA supplementation can protect against memory deficits and inflammatory gene expression in aged rats fed a processed foods diet. Lastly, we showed that while PD consumption increased weight gain in both young and aged rats, this effect was exaggerated in aged rats. Aging was also associated with significant alterations in hypothalamic gene expression, with no impact by DHA on weight gain or hypothalamic gene expression. Together, our data provide novel insights regarding diet-brain interactions by showing that PD consumption impairs cognitive function likely through a neuroimmune mechanism and that dietary DHA can ameliorate this phenomenon.

近几十年来，富含精制碳水化合物、饱和脂肪和缺乏纤维的加工食品饮食 (PD) 的消费有所增加，并可能导致人类慢性病发病率增加和体重增加。这些饮食还被证明可能通过神经免疫相关机制对啮齿动物、非人类灵长类动物和人类的大脑健康和认知功能产生负面影响。然而，帕金森病影响衰老大脑的机制尚不清楚。考虑到老年大脑的基线炎症状态较高，使其更容易受到继发性挑战，这种知识差距至关重要。在这里，我们发现，连续 28 天食用富含精制碳水化合物来源的 PD 会损害老年（24 个月）而非年轻（3 个月）F344 × BN 大鼠的海马和杏仁核依赖性记忆功能。这些记忆缺陷伴随着老年大鼠海马和杏仁核中炎症基因表达的增加，例如 IL-1β、CD11b、MHC II 类、CD86、NLRP3 和补体成分 3。重要的是，我们还表明，当相同的 PD 补充 omega-3 多不饱和脂肪酸 DHA 时，老年大鼠的这些记忆缺陷和炎症基因表达变化得到改善，从而提供了第一个证据，证明补充 DHA 可以预防记忆缺陷和喂食加工食品的老年大鼠的炎症基因表达。最后，我们发现，虽然摄入PD会增加年轻和老年大鼠的体重增加，但这种效应在老年大鼠中被夸大了。衰老还与下丘脑基因表达的显着变化相关，但 DHA 对体重增加或下丘脑基因表达没有影响。 总之，我们的数据表明，PD 摄入可能通过神经免疫机制损害认知功能，而膳食 DHA 可以改善这种现象，从而提供了有关饮食与大脑相互作用的新颖见解。