Title | Gut Microbiota Alterations and Cognitive Impairment Are Sexually Dissociated in a Transgenic Mice Model of Alzheimer's Disease. |
Publication Type | Journal Article |
Year of Publication | 2021 |
Authors | Cuervo-Zanatta, D, Garcia-Mena, J, Perez-Cruz, C |
Journal | J Alzheimers Dis |
Volume | 82 |
Issue | s1 |
Pagination | S195-S214 |
Date Published | 2021 |
ISSN | 1875-8908 |
Keywords | Alzheimer Disease, Animals, Cognitive Dysfunction, Female, Gastrointestinal Microbiome, Humans, Male, Mice, Mice, Transgenic, Sex Characteristics, Spatial Memory |
Abstract | BACKGROUND: Normal aging is accompanied by cognitive deficiencies, affecting women and men equally. Aging is the main risk factor for Alzheimer's disease (AD), with women having a higher risk. The higher prevalence of AD in women is associated with the abrupt hormonal decline seen after menopause. However, other factors may be involved in this sex-related cognitive decline. Alterations in gut microbiota (GM) and its bioproducts have been reported in AD subjects and transgenic (Tg) mice, having a direct impact on brain amyloid-β pathology in male (M), but not in female (F) mice. OBJECTIVE: The aim of this work was to determine GM composition and cognitive dysfunction in M and F wildtype (WT) and Tg mice, in a sex/genotype segregation design. METHODS: Anxiety, short term working-memory, spatial learning, and long-term spatial memory were evaluated in 6-month-old WT and Tg male mice. Fecal short chain fatty acids were determined by chromatography, and DNA sequencing and bioinformatic analyses were used to determine GM differences. RESULTS: We observed sex-dependent differences in cognitive skills in WT mice, favoring F mice. However, the cognitive advantage of females was lost in Tg mice. GM composition showed few sex-related differences in WT mice. Contrary, Tg-M mice presented a more severe dysbiosis than Tg-F mice. A decreased abundance of Ruminococcaceae was associated with cognitive deficits in Tg-F mice, while butyrate levels were positively associated with better working- and object recognition-memory in WT-F mice. CONCLUSION: This report describes a sex-dependent association between GM alterations and cognitive impairment in a mice model of AD. |
DOI | 10.3233/JAD-201367 |
Alternate Journal | J Alzheimers Dis |
PubMed ID | 33492296 |