Aging is associated with a priming of microglia such that they are hypersensitive to further immune challenges. As such high-fat diet during aging can have detrimental effects on cognition that is not seen in the young. However, conflicting findings also suggest that obesity may protect against cognitive decline during aging. Given this uncertainty we aimed here to examine the role of microglia in high-fat, high-sucrose diet (HFSD)-induced changes in cognitive performance in the aging brain. We hypothesised that 8 weeks of HFSD-feeding would alter microglia and the inflammatory milieu in aging and worsen aging-related cognitive deficits in a microglia-dependent manner. We found that both aging and HFSD reduced hippocampal neuron numbers and open field exploration; they also impaired recognition memory. However, the aging-related deficits occurred in the absence of a pro-inflammatory response and the deficits in memory performance persisted after depletion of microglia in the knock-in rat. Our data suggest that mechanisms additional to the acute microglial contribution play a role in aging- and HFSD-associated memory dysfunction.

中文翻译：

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雌性大鼠小胶质细胞缺失的情况下，高脂肪饮食和衰老相关的记忆障碍持续存在


衰老与小胶质细胞的启动有关，因此它们对进一步的免疫挑战高度敏感。因此，衰老过程中的高脂肪饮食会对认知产生不利影响，而这种影响在年轻人中是看不到的。然而，相互矛盾的研究结果也表明，肥胖可以防止衰老过程中的认知能力下降。鉴于这种不确定性，我们的目的是研究小胶质细胞在高脂肪、高蔗糖饮食（HFSD）引起的衰老大脑认知能力变化中的作用。我们假设 8 周的 HFSD 喂养会改变小胶质细胞和衰老过程中的炎症环境，并以小胶质细胞依赖性方式恶化与衰老相关的认知缺陷。我们发现衰老和 HFSD 都会减少海马神经元数量和开放区域探索；他们还损害了识别记忆。然而，与衰老相关的缺陷是在没有促炎症反应的情况下发生的，并且在敲入大鼠的小胶质细胞耗尽后，记忆能力的缺陷仍然存在。我们的数据表明，除了急性小胶质细胞贡献之外的机制在衰老和 HFSD 相关的记忆功能障碍中也发挥着作用。