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Western Diet’ on Emotional, Social and Cognitive Behaviours As Revealed by a Study on Conventional and Serotonin Transporter-Deficient Mice

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Western Diet’ on Emotional, Social and Cognitive Behaviours As Revealed by a Study on Conventional and Serotonin Transporter-Deficient Mice The impact of the ‘Western Diet’ on emotional, social and cognitive behaviours as revealed by a study on conventional and serotonin transporter-deficient mice Citation for published version (APA): Veniaminova, E. (2020). The impact of the ‘Western Diet’ on emotional, social and cognitive behaviours as revealed by a study on conventional and serotonin transporter-deficient mice. Maastricht University. https://doi.org/10.26481/dis.20200305ev Document status and date: Published: 01/01/2020 DOI: 10.26481/dis.20200305ev Document Version: Publisher's PDF, also known as Version of record Please check the document version of this publication: • A submitted manuscript is the version of the article upon submission and before peer-review. There can be important differences between the submitted version and the official published version of record. People interested in the research are advised to contact the author for the final version of the publication, or visit the DOI to the publisher's website. • The final author version and the galley proof are versions of the publication after peer review. • The final published version features the final layout of the paper including the volume, issue and page numbers. Link to publication General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights. • Users may download and print one copy of any publication from the public portal for the purpose of private study or research. • You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal. If the publication is distributed under the terms of Article 25fa of the Dutch Copyright Act, indicated by the “Taverne” license above, please follow below link for the End User Agreement: www.umlib.nl/taverne-license Take down policy If you believe that this document breaches copyright please contact us at: [email protected] providing details and we will investigate your claim. Download date: 06 Oct. 2021 MAASTRICHT UNIVERSITY The impact of the ‘Western diet’ on emotional, social and cognitive behaviours as revealed by a study on conventional and serotonin transporter-deficient mice Ekaterina Veniaminova © E. Veniaminova, Maastricht 2020. The impact of the ‘Western diet’ on emotional, social and cognitive behaviours as revealed by a study on conventional and serotonin transporter-deficient mice Cover: Natalia Nesterova, “A feast in time of plague”, 1993, private collection All rights reserved. No parts of this book may be reproduced or transmitted in any form or by any means, without prior permission in writing by the author, or when appropriate, by the publishers of the publication. The impact of the ‘Western diet’ on emotional, social and cognitive behaviours as revealed by a study on conventional and serotonin transporter-deficient mice DISSERTATION to obtain the degree of Doctor at the Maastricht University, on the authority of the Rector Magnificus, Prof.dr. Rianne M. Letschert in accordance with the decision of the Board of Deans, to be defended in public on Thursday, March 5 th 2020, at 12:00 hours by Ekaterina Veniaminova Promotor: Prof. K.-P. Lesch Co-promotors: Prof. T. Strekalova Prof. D.C. Anthony, University of Oxford Assessment Committee: Prof. Boris W. Kramer (Chairman) Prof. Wilfred T.V. Germeraad Dr. Ehsan S.E. Pishva Prof. Lee Wei Lim, University of Hong Kong Dr. Fay Probert, University of Oxford Contents Propositions ................................................................................... - 7 - Abbreviations ................................................................................ - 9 - Chapter 1. General introduction .................................................. - 14 - 1.1 ‘Western diet’ as an environmental factor in psychiatric morbidities ................................................................................ - 14 - 1.2 Pathophysiological mechanisms of negative effects of Western diet on the brain ....................................................................... - 17 - 1.3 Peripheral effects of Western diet relevant to neuropsychiatric conditions ................................................................................. - 27 - 1.4 Role of decreased function of the serotonin transporter (SERT) in metabolic and mental disorders ............................................ - 33 - 1.5 Studying the effects of Western diet on brain functions using animal models ........................................................................... - 35 - Hypothesis and aim .................................................................. - 39 - References ................................................................................. - 41 - Chapter 2. Autism-like behaviours and memory deficits result from a Western diet in mice ................................................................... - 62 - Chapter 3. Prefrontal cortex inflammation and liver pathologies accompany cognitive and motor deficits following Western diet consumption in non-obese female mice .......................................- 108 - Chapter 4. Metabolic, molecular and behavioural effects of Western diet in serotonin transporter-deficient mice: rescue by heterozygosity? ...................................................................................................- 170 - Chapter 5. General discussion ....................................................- 228 - 5.1 Environmental factors aggravating autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) symptoms: focus on diet ..........................................................- 228 - 5.2 Toll-like receptor 4 (Tlr4) and microglia activation in ASD, ADHD and depression ............................................................. - 231 - 5.3 Oxidative stress and mitochondrial dysfunction in ASD, ADHD and depression ......................................................................... - 237 - 5.4 Interplay between peroxisome proliferator-activated receptors (PPARs), Tlr4, serotonin transporter and insulin receptors activity. ................................................................................................ - 246 - 5.5 Direct and peripheral inflammation-mediated effects of Western diet components on neuroinflammation and brain mitochondrial activity .................................................................................... - 252 - 5.6 The role of Sert deficiency in the interaction between genetic predisposition to psychiatric disorders and diet ...................... - 258 - 5.7 Limitations of animal models of Western diet and Sert deficiency when studying human pathologies .......................................... - 264 - 5.8 Future perspectives ........................................................... - 269 - References ............................................................................... - 270 - Summary ................................................................................... - 295 - Samenvatting ............................................................................. - 298 - Valorization ............................................................................... - 301 - Acknowledgments ...................................................................... - 307 - About the author ....................................................................... - 312 - Propositions 1. The Western diet suppresses social interactions, impairs cognition, induces impulsive and depressive-like behaviours, which are, together, all reminiscent of symptoms of autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) (this thesis) ; 2. The Western diet-induced abnormalities are associated with signs of oxidative stress, microglial activation, decreased gene expression of serotonin transporter in the prefrontal cortex as well as metabolic impairments (this thesis) ; 3. Complete genetic serotonin transporter inactivation exacerbates metabolic, molecular, and the behavioural consequences of the Western diet in aging mice (this thesis) ; 4. Mice with partial genetic serotonin transporter deficiency display a ‘rescued’ phenotype in dietary-induced abnormalities in glucose tolerance, neuroinflammation and hippocampus-dependent behaviour (this thesis) ; 5. Invention of a specific diet might provide relief for patients with co-occurring metabolic and neuropsychiatric disorders, which will decrease costs associated with disability and health management (this thesis, valorization) ; - 7 - 6. Diet might impact on the pathogenesis of other neuropsychiatric disorders not considered in this thesis (for example, psychosis); 7. Other diets such as Mediterranean diet is likely to be protective in adulthood in cases of ADHD/ASD; 8. Gut microbiota has an important role in the interaction between diet and brain dysfunction; 9. “In food excellent medicine can be found, in food bad medicine can be found; good and bad are relative” (Hippocrates, “De Alimento”, 5th-4th century BC) ; 10. “Dilettante gardeners love the spring and summer; real gardeners also love the winter” (Anne Scott-James, “Down to Earth”, 1971) ; 11. “Today’s philosophy questions are tomorrow’s precision science experiments” (Jorge Cham and Daniel Whiteson, “We Have
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