School of Medical Sciences, UNSW Sydney, Sydney, NSW, 2052, Australia.
School of Psychology, UNSW Sydney, Sydney, NSW, 2052, Australia.
Transl Psychiatry. 2020 Mar 13;10(1):92. doi: 10.1038/s41398-020-0774-1.
Diets rich in sugar and saturated fat are associated with cognitive impairments in both humans and rodents with several potential mechanisms proposed. To test the involvement of diet-induced pro-inflammatory signaling, we exposed rats to a high-fat, high-sugar cafeteria diet, and administered the anti-inflammatory antibiotic minocycline. In the first experiment minocycline was coadministered across the diet, then in a second, independent cohort it was introduced following 4 weeks of cafeteria diet. Cafeteria diet impaired novel place recognition memory throughout the study. Minocycline not only prevented impairment in spatial recognition memory but also reversed impairment established in rats following 4 weeks cafeteria diet. Further, minocycline normalized diet-induced increases in hippocampal pro-inflammatory gene expression. No effects of minocycline were seen on adiposity or dietary intake across the experiments. Cafeteria diet and minocycline treatment significantly altered microbiome composition. The relative abundance of Desulfovibrio_OTU31, uniquely enriched in vehicle-treated cafeteria-fed rats, negatively and significantly correlated with spatial recognition memory. We developed a statistical model that accurately predicts spatial recognition memory based on Desulfovibrio_OTU31 relative abundance and fat mass. Thus, our results show that minocycline prevents and reverses a dietary-induced diet impairment in spatial recognition memory, and that spatial recognition performance is best predicted by changes in body composition and Desulfovibrio_OTU31, rather than changes in pro-inflammatory gene expression.
富含糖和饱和脂肪的饮食与人类和啮齿动物的认知障碍有关，提出了几种潜在的机制。为了测试饮食诱导的促炎信号的参与，我们让大鼠暴露于高脂肪、高糖的自助餐厅饮食中，并给予抗炎抗生素米诺环素。在第一个实验中，米诺环素与饮食同时给药，然后在第二个独立的队列中，在 4 周的自助餐厅饮食后引入。自助餐厅饮食在整个研究过程中损害了新的位置识别记忆。米诺环素不仅预防了空间识别记忆的损害，而且还逆转了大鼠在 4 周自助餐厅饮食后建立的损害。此外，米诺环素使饮食诱导的海马体促炎基因表达正常化。米诺环素对脂肪量或饮食摄入量在整个实验中均无影响。自助餐厅饮食和米诺环素处理显著改变了微生物组的组成。在仅用载体处理的喂食自助餐厅的大鼠中，脱硫弧菌_OTU31 的相对丰度独特地增加，与空间识别记忆呈负相关且显著相关。我们开发了一种统计模型，该模型基于脱硫弧菌_OTU31 的相对丰度和脂肪量，可以准确预测空间识别记忆。因此，我们的结果表明，米诺环素可预防和逆转饮食诱导的空间识别记忆损伤，而空间识别性能最好由身体成分和脱硫弧菌_OTU31 的变化来预测，而不是促炎基因表达的变化。
