Han Yuan-Yuan, Li Kang, Hu Jing-Yu, Wu Ji-Chao, Li Xiao, Liu De-Xiang, Li Chu-Hua
Department of Radiology, The Affiliated Panyu Central Hospital of Guangzhou Medical University, Guangzhou, China.
School of Life Science, South China Normal University, Guangzhou, China.
CNS Neurosci Ther. 2024 Dec;30(12):e70164. doi: 10.1111/cns.70164.
Cognitive impairment is a common and feared characteristic of aging processes, and one key mechanism of cognition is hippocampal synaptic structure. Previous studies have reported that gut microbiota dysbiosis occurred in neurodegenerative diseases and other brain disorders with cognitive impairment. However, it is not clear how gender differences affect cognitive impairment in aging processes and whether they affect synaptic structure and gut microbiota. Here, we studied the gender differences in cognitive ability, dendritic morphology, and gut microbiota of adult, middle-, and old-aged rats.
The cognitive ability of rats using was assessed by the Y-maze SAB test, the light/dark discrimination test, and the MWM test. Dendritic morphology was investegated by Golgi staining. Microbiota composition, diversity and richness were analyzed by 16S rRNA gene sequencing.
The results showed that the cognitive ability of old-aged rats was decreased than adult and middle-aged rats in the spontaneous alternation behavior test, the light/dark discrimination test in Y-maze, and the MWM test; males have better cognitive ability than the females for middle-aged rats. The neuronal dendritic structures of CA1, CA3, and DG regions of the hippocampus were damaged to different degrees during aging, and the spine loss of females was more than that of males in CA1 and CA3 of middle-aged rats. In addition, the microbial diversity of gut microbiota was significantly decreased in old-aged male rats; the distribution and composition of microbiota communities were different between male and female rats at different ages.
These findings revealed that cognitive impairment in aged rats might result from dendritic damage in the hippocampus and gut microbiota dysbiosis, which provides direct evidence that gender differences in dendritic damage and gut microbiota dysbiosis might associate with cognitive impairment in naturally aged rats.
认知障碍是衰老过程中常见且令人担忧的特征,认知的一个关键机制是海马突触结构。先前的研究报道,在神经退行性疾病和其他伴有认知障碍的脑部疾病中会出现肠道微生物群失调。然而,尚不清楚性别差异如何影响衰老过程中的认知障碍,以及它们是否会影响突触结构和肠道微生物群。在此,我们研究了成年、中年和老年大鼠在认知能力、树突形态和肠道微生物群方面的性别差异。
通过Y迷宫SAB试验、明暗辨别试验和莫里斯水迷宫试验评估大鼠的认知能力。通过高尔基染色研究树突形态。通过16S rRNA基因测序分析微生物群的组成、多样性和丰富度。
结果表明,在自发交替行为试验、Y迷宫中的明暗辨别试验和莫里斯水迷宫试验中,老年大鼠的认知能力低于成年和中年大鼠;中年大鼠中,雄性的认知能力优于雌性。衰老过程中,海马体CA1、CA3和DG区的神经元树突结构受到不同程度的损伤,中年大鼠CA1和CA3区雌性的树突棘损失多于雄性。此外,老年雄性大鼠肠道微生物群的微生物多样性显著降低;不同年龄的雄性和雌性大鼠微生物群落的分布和组成不同。
这些发现表明,老年大鼠的认知障碍可能是由海马体树突损伤和肠道微生物群失调引起的,这提供了直接证据,表明树突损伤和肠道微生物群失调的性别差异可能与自然衰老大鼠的认知障碍有关。