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Research lines Structural and Functional Plasticity of the Nervous System

  • Dr H.J. (Harm) Krugers - Understanding how (early life) stress alters brain and behaviour

    In our daily lives, we are regularly exposed to stressful and emotionally arousing events. While most people can adapt well to such events, some individuals are at risk for developing stress-related disorders, like major depression, anxiety disorders and post-traumatic stress-disorder.

    Coping with stressful events requires appropriate cognitive processing in order to promote behavioural adaptation. The overarching goal of our lab is to understand how individuals adapt to stressful and emotionally arousing events and how resilience and vulnerability to develop stress-related disorders is determined. 
    Our research can roughly be divided into three themes:

    1. Understand how stress and stress-hormones modulate learning, memory and fear
    2. Understand the mechanisms how stress early in life determines learning and memory and fear over the life span and over generations;
    3. Understand the mechanisms how early life experiences affect social behavior later in life.

    To address these questions, the Krugers lab exploits and combines animal behavior with electrophysiology, biochemical tools, pharmacology, molecular tools and cellular imaging. More recently, the lab also performs translational studies on fear and fear generalization in humans and healthy aging in humans.

    Harm Krugers is Associate Professor at SILS. He is Program Director of the Research Master Brain and Cognitive Sciences, board member of Amsterdam Brain and Cognition (ABC); Board member of the Society for Interdisciplinary Behavioural Research (SIGO) and member of the executive board of FENS.

    Current lab members

    Dr Erica Beretta
    Niek Brosens, MSc
    Jeniffer Sanguino Gómez, MSc. (guest)

    Past lab members

    Sylvie Lesuis
    Hui Xiong
    Marit Arp
    Dr Judith ter Horst
    Ming Zhou
    Sofia Kanatsou
    Deborah Alfarez
    Zhenwei Pu
    Felisa van Hasselt
    Olof Wiegert

    Dr. H.J. (Harm) Krugers

    Faculty of Science

    Swammerdam Institute for Life Sciences

  • Dr A. (Aniko) Korosi - Programming of mental and metabolic health by early-life stress focus on inflammation and nutrition

    Research aims

    Early life is a sensitive period of development. When this period is disturbed by exposure to childhood adversity, it can have a lasting impact on the adult we become, on mental and physical health, increasing the vulnerability to develop a large range of disorders (e.g. depression, cognitive decline and obesity). Because prevention of early-life stress is often difficult, a better understanding of the mechanisms that underlie the early programming of the brain, behavior and body is needed.

    We study the effects of early-life stress in the context of wild type, but also Alzheimer mouse models. We have recently found that exposure to early-life stress is associated with impaired learning and memory, altered neuroimmune system, altered responses to amyloid and altered fat and leptin system.
    Importantly, we have recently identified early nutritional interventions with essential PUFAs or with methyl donor micronutrients, that were able to protect against some of the detrimental effects of early-life stress exposure. The exact mechanisms underlying the beneficial effects of such diet, and whether this could be considered also in the context of Alzheimer’s disease, are among our current research interests.
    The main goal of our research group is to better understand the biological mechanisms and environmental factors involved in brain programming by stressful early-life experiences and to test the efficacy of nutritional interventions. We focus on essential nutrients and early dietary interventions in particular. The translational value of this approach is high as nutrition is typically non-invasive, cheap and easily applicable.
    We aim to identify how the various components of the early-life environment, including stress-hormones, early nutrition and inflammatory modulators act synergistically in programming the brain and body.
    We study these aspects across species, in mice, humans and fish.

    Mice
    We use wild type as well as transgenic mice (e.g. Alzheimer’s disease mouse model) and an established mouse model of early-life stress. We study if and how early-life stress-induces alterations in brain structure and function and metabolic characteristics under a basal state or after various challenges (e.g. immune challenge, or metabolic challenges) and study in detail the involvement of various cell types of the brain (neurons, astrocytes, microglia), in vivo and in vitro. Within the brain, our main focuses are on the hippocampus and hypothalamus, very plastic brain regions involved in learning and memory, in stress regulation and energy homeostasis, and focus on various forms of brain plasticity, related to hippocampal neurogenesis, microglia and astrocytes.

    Human
    - We have set up the Amsterdam mother milk cohort (AMS) to study the effects of stress on the composition of human breastmilk, in collaboration with Prof Hans van Goudoever (AUMC).
    - We work in collaboration with AUMC (Dr. S. de Rooij) on the Dutch Famine birth cohort and ABCD cohorts to understand the biological characteristics (lipid and immune profile) of blood, aimed at understanding mechanisms and possibly identifying biomarkers of early stress exposure.

    Fish
    Work in collaboration with WUR (Dr. B. Pollux) on novel placental fish species to study the evolution of maternal effects on the offspring.

    If you are interested in more details, my personal website is: https://akorosi.wixsite.com/korosigroup

    Aniko Korosi is Associate Professor at SILS. She is coordinator of the Neuroscience master track (PPP, Psychopathophysiology) of the Research Master biomedical Sciences, treasurer and member of the executive board of the European brain and behavior society (EBBS), member of the executive board of the Dutch Neuroscience meeting (DNM) and chair of DNM2020/2021. Member of the ECNP nutrition network, Aniko Korosi is member of the editorial board of several recognized journals, including eNeuro and Frontiers in Neuroenergenetics, Nutrition and Brain health, and she regularly acts as evaluation and advisory board member for several national and international grant agencies and research councils.

    Current lab members

    Kitty Reemst
    Silvie Ruigrok
    Jorine Geertsema
    Janssen Kotah
    Hannah Juncker

    Guests

    Dr. Veronica Begni (Italy)-postdoc
    Simone de Luca (Australia)

    Past lab members

    Dr Eva Naninck
    Kit-Yi Yam
    Lianne Hoeijmakers
    Maralinde Abbink
    Dr Livia Clemente
    Dr Claudia Sestito (collaborative postdoc with Dr. Vivi Heine, Free University, Amsterdam)

    Dr. A. (Aniko) Korosi

    Faculty of Science

    Swammerdam Institute for Life Sciences

  • Dr C.P. (Carlos) Fitzsimons - Common molecular mechanisms of brain insults affecting the hippocampus

    Brain insults that involve the hippocampus, like epilepsy, stroke, neuroinflammation, chronic stress and traumatic brain injury, are commonly associated with cognitive impairment and mood disorders, and contribute to the pathology of neurodegenerative diseases such as Alzheimer’s disease. These insults can affect several forms of structural plasticity in the brain, affecting specific cellular populations, modifying the communication between neurons and thereby affect important neuronal circuits, which compromises hippocampal network function and hampers hippocampus-dependent behavior.

    The focus of the Fitzsimons lab is to identify common mechanisms by which brain insults affect cognition. For this, we focus on a group of insults that modify the proliferation and function of neural stem cells, resulting in the presence of abnormal neurons, circuits, and cellular alterations associated with neurodegeneration and cognitive impairment.

    Detailed information about our past and ongoing activities, experimental approaches used in the lab and scientific expertise can be found at our lab’s website: https://www.fitzsimonslab.eu/

    Current international collaborations include:

    • Astrogliosis and neuroinflammation: Matthew Holt, Lab of Glia Biology, VIB-KU Leuven Center for Brain and Disease Research, and Adrian Liston, Babraham Institute, Cambridge, UK.
    • Biology of small non-coding RNAs: Davide de Pietri Tonelli, Italian Institute of Technology, Genoa, Italy.
    • Contribution of reactive neural stem cells to hippocampal pathology: Juan Manuel Encinas, Achucaro Basque Center for Neuroscience, Bilbao, Spain.

    Carlos Fitzsimons is member of the editorial board of several recognized journals, including Scientific Reports, Frontiers in Neuroscience, Frontiers in Cellular Neuroscience and Frontiers in Molecular Neuroscience and he regularly acts as evaluation and advisory board member for several European and international research councils.

    Current lab members

    Dr Oihane Abiega Etxabe (guest)

    Past lab members

    Dr Marijn Schouten
    Dr Pascal Bielefeld

    Dr. C.P. (Carlos) Fitzsimons

    Faculty of Science

    Swammerdam Institute for Life Sciences

  • Dr J.D. (Joram) Mul - Adaptations in the brain underlying the effects of physical (in)activity on cognition and stress-related behaviour

    What do we do?

    Our main goal is to elucidate adaptations in the brain that underlie the beneficial and maladaptive effects of physical (in)activity on stress-related and cognitive behaviour.

    Why do we do this?

    Elucidating mechanisms by which repeated physical activity (i.e. exercise training) promotes resilience, the brain’s ability to cope with prolonged stress exposure, while maintaining normal psychological functioning, is a major research challenge given the high prevalence of stress-related mental disorders, including depression and PTSD. Exercise training also improves cognitive behavior, and elucidating the underlying mechanisms can lead to new therapies to improve cognition, or halt age-related cognitive decline.

    How do we do this?

    We perform both preclinical and clinical studies, resulting in a unique translational approach that increases our knowledge of beneficial and maladaptive brain adaptations during physical activity and inactivity, respectively.

    • We use the preclinical voluntary wheel running (VWR) model to gain mechanistic insight into how physical (in)activity produces adaptations in the reward-related brain circuitry and hippocampus that modulate stress sensitivity and cognition. To do this, a wide variety of behavioral and molecular techniques (e.g. qPCR, immunohistochemistry, RNA sequencing, synaptic function analysis) is used. Our interest includes determining the functional consequences of VWR on adult hippocampal neurogenesis.
    • We use functional Magnetic Resonance Imaging (fMRI) to visualize the impact of behavioral treatment, including exercise training, on brain function in subjects with stress-related psychiatric disorders. 
    • We use wearable technology (e.g. wrist worn accelerometers) to assess the role of physical (in)activity in the development and relapse of stress-related psychiatric disorders. 


    Our work has received financial support from the following sources:
    Urban Mental Health Institute
    Amsterdam Neuroscience
    Dr. J.L. Dobberke Foundation
    Amsterdam Brain and Cognition

    Lab personnel

    Amber Koert, PhD candidate, 2020-2024

    Dr. J.D. (Joram) Mul

    Faculty of Science

    Swammerdam Institute for Life Sciences