Gender Differences in Dendritic Damage, Gut Microbiota Dysbiosis, and Cognitive Impairment During Aging Processes

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.