Journal of Alzheimer's Disease
Published on Journal of Alzheimer's Disease (https://www.j-alz.com)

Home > Gut Microbiota Alterations and Cognitive Impairment Are Sexually Dissociated in a Transgenic Mice Model of Alzheimer's Disease.

TitleGut Microbiota Alterations and Cognitive Impairment Are Sexually Dissociated in a Transgenic Mice Model of Alzheimer's Disease.
Publication TypeJournal Article
Year of Publication2021
AuthorsCuervo-Zanatta, D, Garcia-Mena, J, Perez-Cruz, C
JournalJ Alzheimers Dis
Volume82
Issues1
PaginationS195-S214
Date Published2021
ISSN1875-8908
KeywordsAlzheimer 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.

DOI10.3233/JAD-201367
Alternate JournalJ Alzheimers Dis
PubMed ID33492296
E-mail Icon
Comment Icon
  • Comment
Bookmark Icon Bookmark Recommend Icon Recommend Follow Icon Follow
  • Comment
| Bookmark | Recommend | Follow

Source URL: https://www.j-alz.com/content/gut-microbiota-alterations-and-cognitive-impairment-are-sexually-dissociated-transgenic-mice