Age-related shifts in gut microbiota contribute to cognitive decline in aged rats
Age-related shifts in gut microbiota contribute to cognitive decline in aged rats
复制标题
肠道微生物群与年龄相关的变化导致老年大鼠认知能力下降
DOI：
10.18632/aging.103093
复制
发表时间：
2020-05-15
期刊：
影响因子：
5.2
通讯作者：
Zhang, Ce
中科院分区：
文献类型：
--
作者：
Li, Yanli;Ning, Li;Zhang, Ce
随着年龄的增长，老年人的认知功能下降，同时，老年人的肠道菌群也发生了明显的变化。虽然以前的研究已经报道了肠道微生物群对学习和记忆的影响，但所有的报道都是基于各种人工干预来改变肠道微生物群，而不涉及衰老的生物学特征。在这里，我们研究了老年肠道微生物群对认知功能的影响，通过使用粪便微生物群移植（FMT）从老年大鼠到年轻大鼠。结果表明，FMT可损害幼年大鼠的认知行为，降低内侧前额叶皮质和海马的区域均一性，改变突触结构，减少树突棘，降低脑源性神经营养因子（BDNF）、N-甲基-D-天冬氨酸受体NR 1亚单位和突触素的表达，增加晚期糖基化终产物（AGEs）和AGEs受体（RECEPTOR）的表达。FMT引起的所有这些行为、脑结构和功能改变反映了认知能力的下降。此外，FMT增加了年轻大鼠中促炎细胞因子和氧化应激的水平，表明炎症和氧化应激可能是衰老中肠道相关认知能力下降的基础。这项研究为肠道微生物群对正常衰老期间认知能力下降的贡献提供了直接证据，并表明恢复老年人的微生物群稳态可能会改善认知功能。
Cognitive function declines during the aging process, meanwhile, gut microbiota of the elderly changed significantly. Although previous studies have reported the effect of gut microbiota on learning and memory, all the reports were based on various artificial interventions to change the gut microbiota without involvement of aging biological characteristics. Here, we investigated the effect of aged gut microbiota on cognitive function by using fecal microbiota transplantation (FMT) from aged to young rats. Results showed that FMT impaired cognitive behavior in young recipient rats; decreased the regional homogeneity in medial prefrontal cortex and hippocampus; changed synaptic structures and decreased dendritic spines; reduced expression of brain-derived neurotrophic factor (BDNF), N-methyl-D-aspartate receptor NR1 subunit, and synaptophysin; increased expression of advanced glycation end products (AGEs) and receptor for AGEs (RAGE). All these behavioral, brain structural and functional alterations induced by FMT reflected cognitive decline. In addition, FMT increased levels of pro-inflammatory cytokines and oxidative stress in young rats, indicating that inflammation and oxidative stress may underlie gut-related cognitive decline in aging. This study provides direct evidence for the contribution of gut microbiota to the cognitive decline during normal aging and suggests that restoring microbiota homeostasis in the elderly may improve cognitive function.