Antibiotic-induced gut microbiota depletion from early adolescence exacerbates spatial but not recognition memory impairment in adult male C57BL/6 mice with Alzheimer-like disease

Abstract

Gut microbiota dysbiosis is associated with cognitive dysfunctions and Alzheimer’s disease (AD). This study set out to better understand the relationship between gut microbiota depletion and cognitive abilities in mice with or without Alzheimer-like disease. Male C57BL/6 mice from early adolescence received an antibiotic cocktail, and then in adulthood, animals were subjected to a stereotaxic surgery to induce Alzheimer-like disease using amyloid-beta (Aβ) 1–42 microinjection. To assess cognitive functions in mice, three behavioural tests including the Y maze, object recognition, and Morris water maze were used. We also measured brain-derived-neurotrophic factor (BDNF), tumour-necrosis factor (TNF)-α, interleukin (IL)-6, and Aβ42 in the brain. Our findings showed that antibiotics treatment impaired object recognition memory, whereas did not alter spatial memory in healthy mice. Antibiotics treatment in mice significantly exacerbated spatial memory impairment following the induction of AD in both the Y maze and Morris water maze test. There were significant correlations between these behavioural tests. In addition, healthy animals treated with antibiotics displayed a significant reduction in brain IL-6. We observed that antibiotics treatment significantly decreased both cytokines TNF-α and IL-6 in the brain of AD-induced mice. However, no alterations were found in brain BDNF levels following both antibiotics treatment and AD induction. These findings show that antibiotic-induced gut microbiota depletion from early adolescence to adulthood can impair cognitive abilities in mice with or without Alzheimer-like disease. Overall, this study suggests that gut microbiota manipulation from early adolescence to adulthood may adversely affect the normal development of cognitive functions.