Ketogenic diet changes microglial morphology and the hippocampal lipidomic profile differently in stress susceptible versus resistant male mice upon repeated social defeat.

Autor: González Ibáñez F; Axe Neurosciences, Centre de Recherche du CHU de Québec-Université Laval, Québec, Quebec, Canada; Département de Médecine Moléculaire, Université Laval, Québec, Quebec, Canada; Division of Medical Sciences, University of Victoria, Victoria, British Columbia, Canada., Halvorson T; Division of Medical Sciences, University of Victoria, Victoria, British Columbia, Canada; Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada., Sharma K; Axe Neurosciences, Centre de Recherche du CHU de Québec-Université Laval, Québec, Quebec, Canada; Département de Médecine Moléculaire, Université Laval, Québec, Quebec, Canada; Department of Chemistry, Purdue University, West Lafayette, Indiana, United States., McKee CG; Division of Medical Sciences, University of Victoria, Victoria, British Columbia, Canada., Carrier M; Axe Neurosciences, Centre de Recherche du CHU de Québec-Université Laval, Québec, Quebec, Canada; Département de Médecine Moléculaire, Université Laval, Québec, Quebec, Canada; Division of Medical Sciences, University of Victoria, Victoria, British Columbia, Canada., Picard K; Axe Neurosciences, Centre de Recherche du CHU de Québec-Université Laval, Québec, Quebec, Canada; Département de Médecine Moléculaire, Université Laval, Québec, Quebec, Canada; Division of Medical Sciences, University of Victoria, Victoria, British Columbia, Canada., Vernoux N; Axe Neurosciences, Centre de Recherche du CHU de Québec-Université Laval, Québec, Quebec, Canada., Bisht K; Axe Neurosciences, Centre de Recherche du CHU de Québec-Université Laval, Québec, Quebec, Canada; Département de Médecine Moléculaire, Université Laval, Québec, Quebec, Canada; Department of Chemistry, Purdue University, West Lafayette, Indiana, United States., Deslauriers J; Faculté de Pharmacie, Université Laval, Québec, Quebec, Canada., Lalowski M; Department of Gene Expression, Institute of Molecular Biology and Biotechnology, Faculty of Biology, Adam Mickiewicz University, Poznań, Poland; Biochemistry/Developmental Biology and HiLIFE, Meilahti Clinical Proteomics Core Facility, University of Helsinki, Finland., Tremblay MÈ; Axe Neurosciences, Centre de Recherche du CHU de Québec-Université Laval, Québec, Quebec, Canada; Département de Médecine Moléculaire, Université Laval, Québec, Quebec, Canada; Division of Medical Sciences, University of Victoria, Victoria, British Columbia, Canada; Neurology and Neurosurgery Department, McGill University, Montréal, Quebec, Canada; Department of Biochemistry and Molecular Biology, The University of British Columbia, Vancouver, British Columbia, Canada; Centre for Advanced Materials and Related Technology (CAMTEC), University of Victoria, British Columbia, Canada. Electronic address: evetremblay@uvic.ca.
Jazyk: angličtina
Zdroj: Brain, behavior, and immunity [Brain Behav Immun] 2023 Nov; Vol. 114, pp. 383-406. Date of Electronic Publication: 2023 Sep 07.
DOI: 10.1016/j.bbi.2023.09.006
Abstrakt: Psychological stress confers an increased risk for several diseases including psychiatric conditions. The susceptibility to psychological stress is modulated by various factors, many of them being modifiable lifestyle choices. The ketogenic diet (KD) has emerged as a dietary regime that offers positive outcomes on mood and health status. Psychological stress and elevated inflammation are common features of neuropsychiatric disorders such as certain types of major depressive disorder. KD has been attributed anti-inflammatory properties that could underlie its beneficial consequences on the brain and behavior. Microglia are the main drivers of inflammation in the central nervous system. They are known to respond to both dietary changes and psychological stress, notably by modifying their production of cytokines and relationships among the brain parenchyma. To assess the interactions between KD and the stress response, including effects on microglia, we examined adult male mice on control diet (CD) versus KD that underwent 10 days of repeated social defeat (RSD) or remained non-stressed (controls; CTRLs). Through a social interaction test, stressed mice were classified as susceptible (SUS) or resistant (RES) to RSD. The mouse population fed a KD tended to have a higher proportion of individuals classified as RES following RSD. Microglial morphology and ultrastructure were then analyzed in the ventral hippocampus CA1, a brain region known to present structural alterations as a response to psychological stress. Distinct changes in microglial soma and arborization linked to the KD, SUS and RES phenotypes were revealed. Ultrastructural analysis by electron microscopy showed a clear reduction of cellular stress markers in microglia from KD fed animals. Furthermore, ultrastructural analysis showed that microglial contacts with synaptic elements were reduced in the SUS compared to the RES and CTRL groups. Hippocampal lipidomic analyses lastly identified a distinct lipid profile in SUS animals compared to CTRLs. These key differences, combined with the distinct microglial responses to diet and stress, indicate that unique metabolic changes may underlie the stress susceptibility phenotypes. Altogether, our results reveal novel mechanisms by which a KD might improve the resistance to psychological stress.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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