Author, as appears in the article.: Yanguas-Casas, Natalia; Torres, Cristina; Crespo-Castrillo, Andrea; Diaz-Pacheco, Sonia; Healy, Kiera; Stanton, Catherine; Chowen, Julie A.; Garcia-Segura, Luis M.; Angeles Arevalo, Maria; Cryan, John F.; de Ceballos, Maria L.;
Department: Bioquímica i Biotecnologia
URV's Author/s: Torres Fuentes, Cristina
Keywords: Transgenic mouse model Tgapp mice Sex differences Risk Phagocytosis Obesity Microglia Microbiota Memory deficits Inflammation Driving-force Diet Cytokines Cognitive impairment Brain Anxiety Amyloid pathology Alzheimers-disease Alzheimer's disease Akkermansia-muciniphila
Abstract: Long-term high-fat diet (HFD) consumption commonly leads to obesity, a major health concern of western societies and a risk factor for Alzheimer's disease (AD). Both conditions present glial activation and inflammation and show sex differences in their incidence, clinical manifestation, and disease course. HFD intake has an important impact on gut microbiota, the bacteria present in the gut, and microbiota dysbiosis is associated with inflammation and certain mental disorders such as anxiety. In this study, we have analyzed the effects of a prolonged (18 weeks, starting at 7 months of age) HFD on male and female mice, both wild type (WT) and TgAPP mice, a model for AD, investigating the behavioral profile, gut microbiota composition and inflammatory/phagocytosis-related gene expression in hippocampus. In the open-field test, no overt differences in motor activity were observed between male and female or WT and TgAPP mice on a low-fat diet (LFD). However, HFD induced anxiety, as judged by decreased motor activity and increased time in the margins in the open-field, and a trend towards increased immobility time in the tail suspension test, with increased defecation. Intriguingly, female TgAPP mice on HFD showed less immobility and defecation compared to female WT mice on HFD. HFD induced dysbiosis of gut microbiota, resulting in reduced microbiota diversity and abundance compared with LFD fed mice, with some significant differences due to sex and little effect of genotype. Gene expression of proinflammatory/phagocytic markers in the hippocampus were not different between male and female WT mice, and in TgAPP mice of both sexes, some cytokines (IL-6 and IFN gamma) were higher than in WT mice on LFD, more so in female TgAPP (IL-6). HFD induced few alterations in mRNA expression of inflammatory/phagocytosis-related genes in male mice, whether WT (IL-1 beta, MHCII), or TgAPP (IL-6). However, in female TgAPP, altered gene expression returned towards control levels following prolonged HFD (IL-6, IL-12 beta, TNF alpha, CD36, IRAK4, PYRY6). In summary, we demonstrate that HFD induces anxiogenic symptoms, marked alterations in gut microbiota, and increased expression of inflammatory genes, except for female TgAPP that appear to be resistant to the diet effects. Lifestyle interventions should be introduced to prevent AD onset or exacerbation by reducing inflammation and its associated symptoms; however, our results suggest that the eventual goal of developing prevention and treatment strategies should take sex into consideration.
Thematic Areas: Odontología Neurosciences Neurology Medicina ii Medicina i Interdisciplinar General medicine Engenharias ii Educação física Clinical neurology Ciências biológicas iii Ciências biológicas ii Ciências biológicas i Biotecnología
licence for use: https://creativecommons.org/licenses/by/3.0/es/
Author's mail: cristina.torres@urv.cat
Author identifier: 0000-0002-2917-6910
Record's date: 2024-07-27
Papper version: info:eu-repo/semantics/publishedVersion
Link to the original source: https://www.sciencedirect.com/science/article/pii/S0969996121002448?via%3Dihub
Licence document URL: https://repositori.urv.cat/ca/proteccio-de-dades/
Papper original source: Neurobiology Of Disease. 159
APA: Yanguas-Casas, Natalia; Torres, Cristina; Crespo-Castrillo, Andrea; Diaz-Pacheco, Sonia; Healy, Kiera; Stanton, Catherine; Chowen, Julie A.; Garcia-Se (2021). High-fat diet alters stress behavior, inflammatory parameters and gut microbiota in Tg APP mice in a sex-specific manner. Neurobiology Of Disease, 159(), -. DOI: 10.1016/j.nbd.2021.105495
Article's DOI: 10.1016/j.nbd.2021.105495
Entity: Universitat Rovira i Virgili
Journal publication year: 2021
Publication Type: Journal Publications
Repositori URV