Various environmental cues affect the brain and particularly when experienced during the early life period, they govern susceptibility to disease. This ‘imprinting’ has long-lasting effects. Indeed the quality of perinatal environment and postnatal experience is known to predict vulnerability to psychopathologies like depression and anxiety, as well as cognitive function in the adult. However very little is known about the exact mechanism by which early-life experience imprints the brain.

In the lab we aim to unravel the molecular and epigenetic mechanisms by which early-life experiences persistently alter brain plasticity, thereby making an individual either vulnerable or resilient to (stress-related) psychopathologies. My research focuses on how transient early-life experiences shape brain structure and function and therefore our behavior, in a long-lasting and sex-dependent manner (fig 1).

Research lines

(1) Acute and lasting effects of early-life stress on cognitive function, stress response and the related structural and functional plasticity of the brain in male and female mice.

(2) Epigenetic mechanisms governing the lasting effects of early-life stress on gene expression. We study in detail the mechanisms underlying the long-lasting reduction of neuronal plasticity induced by early-life stress. In particular, we are interested in the effects of chronic early-life stress on neurogenesis in the dentate gyrus of the hippocampus (DG), an amazing form of brain plasticity in the adult mammalian brain (figure 2). This plasticity has been implicated in cognitive functions such as learning and memory. Our research is of high clinical relevance as long lasting changes in the level of neurogenesis and coping with stress may predispose to stress-related psychopathologies like depression, anxiety and possibly dementia which belong to the most common and severe human psychopathologies in today’s western society.

(3) Adult-generated neurons, originating from the subventricular zone (SVZ) and integrating in the olfactory system participate in olfactory memory formation. This process is crucial for social sex-specific interactions, such as mating and parenting. Therefore we investigate if chronic postpartum stress reduces adult neurogenesis in the maternal olfactory system, affecting the ability of the dam to express maternal behavior

Previous research experience

During my Postdoctoral research carried out at the University of California Irvine in Prof. Baram’s lab, I investigated the mechanisms involved in the programming of the stress system by early-life experience, resulting in resilience to depression and similar stress-related disorders. I focused on the plasticity of the innervation of the corticotropin releasing factor (CRH) cells in the paraventricular nucleus of the hypothalamus and on epigenetic mechanisms. During my PhD research, conducted at the Radboud University Nijmegen under Prof. Roubos and Dr. Kozicz from the Radboud University Nijmegen and Prof. Olivier from the University of Utrecht. The underlying question of my research was how CRH and the CRH-related peptide Urocortin1 (Ucn1), acting via CRH receptors, collaborate in stress adaptation. During my Master thesis, executed at the Radboud University Nijmegen (funded by a European scholarship promoting international exchange; Erasmus project). This focused on the role of Parvalbumin (a calcium binding protein) in a model of absence epilepsy (WAG/Rij rat) in collaboration with Prof. Roubos, Dr. Veening and Dr. van Luitelaar.

    In the lab we have experience in a significant number of methodologies, ranging from molecular to behavioral approaches, allowing studying of complex scientific questions from many different angles. We have expertise in quantitative neuoranatomy using immunocytochemistry (free floating and on slides), radioactive and non-radioactive in situ hybridization and confocal microscopic imaging. We employ biochemical methods including western blots from dissected and micro-dissected brain regions using punches from adult and developing rodent brains. We are also familiar with molecular biological techniques including cloning and tagging. In addition, we implement methods used in Epigenetics, including chromatin immunoprecipitation (ChIP) and employ RIA, stereotactic surgery (both for electrode implantation as well as injections directly into the hypothalamus), cognitive and emotional behavioral tests (Morris water maze, object recognition task, open field test and observation of maternal behavior). We also use in vitro models including organotypic slice cultures of hypothalamus and hippocampus.

National and international collaborations :

• Prof Dr TZ Baram University of California Irvine, CA, USA
• Prof Dr P Sassone-Corsi University of California Irvine, CA, USA
• Prof Dr M Wood University of California Irvine, CA, USA
•  
• Prof Dr TL Horvath Yale School of Medicine, New Haven, CT, USA
• Prof Dr XB Gao Yale School of Medicine, New Haven, CT, USA
• Dr ZW Liu Yale School of Medicine, New Haven, CT, USA
•  
• Prof Dr W Saltzman University of California Riverside, CA, USA
• Dr TR de Jong University of California Riverside, CA, USA
•  
• Dr B Gaszner University of Pecs, Pecs Hungary
•  
• Prof Dr. EW Roubos Radboud University Nijmegen, Nijmegen, the Netherlands
• Dr T Kozicz Radboud University Nijmegen, Nijmegen, the Netherlands
• Dr JG Veening Radboud University Nijmegen, Nijmegen, the Netherlands
•  
• Prof Dr B Olivier University of Utrecht, Utrecht, the Netherlands
• Dr L Groenink University of Utrecht, Utrecht, the Netherlands
• Prof Dr R de Kloet Leiden University, Leiden, the Netherlands

Educational contribution in the following Master courses

• Advanced Psychopathology
• Experimental Neurobiology
• Early-life related vulnerability to adult onset disorders

Group members

• Eva Naninck, PhD student
• Robin Broersen, Bachelor student

Selected publications

• A. Korosi, E. Naninck, C.A. Oomen, M. Schouten, H. Krugers, C. Fitzsimons, PJ. Lucassen
  Early-life stress mediated modulation of adult neurogenesis and behavior
  Behav Brain Res 2011, in press.

• A. Korosi*, S. McClelland*, J. Cope, A. Ivy and T. Z. Baram (2011)
  Emerging roles of epigenetic mechanisms in the enduring effects of neonatal stress and experience on learning and memory    (* equal contribution to the manuscript)
  Neurobiology of Learning and Memory; special issue Epigenetics and memory (96:79-88)

• A. Korosi, M. Shanabrough, S. McClelland, Z-W. Liu, E. Borok,
  X-B. Gao, T.L. Horvath and T.Z. Baram (2010)
  Early-life experience reduces excitation to stress-responsive hypothalamic neurons
  and re-programs the expression of corticotropin releasing hormone.
  J Neuroscience (30: 703-713)

• A. Korosi and T.Z. Baram (2010)
  Plasticity of the stress response early-in life: mechanisms and significance
  Developmental Psychobiology (52:661-670)

• A. Korosi and T.Z. Baram (2009)
  The pathways from mother's love to baby's future. Frontiers in Behavioral Neuroscience (3:27)

• B. Gaszner, D.C.W.A. Van Wijk, A. Korosi, R. Józsa, E.W. Roubos and T. Kozicz (2009)
  Diurnal Expression of Period 2 Protein and Urocortin 1 in Neurons of the Non-preganglionic Edinger-Westphal Nucleus in the Rat
  Stress (12:115-24)

• A. Korosi and T.Z. Baram (2008)
  The central corticotropin releasing factor system during development and adulthood
  European Journal of Pharmacology (583:204-14)

• A. Korosi*, B. Gaszner*, M. Palkovits, E. W. Roubos and T. Kozicz (2007)
  Neuropeptide Y activates urocortin 1 neurons in the non-preganglionic Edinger-Westphal nucleus
  J. Comparative Neurology 500: 708-19 (* equal contribution to the manuscript)

• A. Korosi, T. Kozicz, J.Richter, J.G. Veening, B. Olivier and E.W. Roubos (2007)
  Corticotropin-releasing factor, urocortin 1 and their receptors in the mouse spinal cord
  J. Comparative Neurology 502:973-989

• A. Korosi, T. Kozicz, J.G. Veening, A. Dirks, L. Groenink,
  J. van der Gugten, E.W. Roubos and B. Olivier (2006)
  Distribution of CRF receptor 1 and 2 mRNAs in the CRF-overexpressing mouse brain.
  Brain Res., 1072:46-54

• A. Korosi, S. Schotanus, B. Olivier, E.W. Roubos and T. Kozicz (2005)
  Chronic stress-induced response of urocortin 1 neurons in the Edinger-Westphal
  nucleus in the mouse. Brain Res., 1046: 172-179.

• T. Kozicz, A. Korosi, C. Korsman, D.T.W.M. Tilburg-Ouwens,
  L. Groenink, E.W. Roubos and B. Olivier (2004)
  Urocortin expression in the Edinger-Westphal nucleus is down-regulated in the transgenic
  mice overexpressing neuronal corticotropin releasing factor. Neurosci. 123: 589-594.

• M.C. van de Bovenkamp-Janssen, A. Korosi, J.G. Veening,
  W. Scheenen, E. van Luijtelaar and E.W. Roubos (2004)
  Neuronal parvalbumin and absence epilepsy in WAG/Rij rats. In: The WAG/Rij model of Absence Epilepsy: The Nijmegen-Russion Federation Papers (G. Luijtelaar, G.D. Kutznetsova, A. Coenen, S.A. Chepurnov, Eds.). Nijmegen Institute for Cognition and Information. Nijmegen, pp. 29-36.

• A. Dirks, L. Groenink, J.A. Bouwknecht, T.H. Hijzen, J. van der Gugten,E. Ronken, J.S. Verbeek,
  J.G. Veening, P.J.W.C. Dederen, A. Korosi, L.F. Schoolderman, E.W. Roubos and B. Olivier (2002)
  Overexpression of corticotropin-releasing hormone in transgenic mice and chronic stress-like autonomic and physiological alterations. Eur. J. Neurosci. 16: 1751-1760.




• Recent media attention Amsterdam FM radio, 8th of May 2011 11:00-12:00u; Swammerdam wetenschap te Amsterdam, Radio interview with Eva Naninck about epigenetics.

Curriculm Vitae

• 2010-present    Assistant professor position Swammerdam Institute for Life Sciences,
  Center for Neuroscience University of Amsterdam
• 2006-2010    Postdoctoral research position Department of Pediatrics and Anatomy/Neurobiology at the University of California Irvine, Irvine, CA USA with Prof. Dr. T.Z.Baram
• 2006    Postdoctoral research position Department of Cellular Animal Physiology at the Radboud University Nijmegen, Nijmegen the Netherlands with Prof Dr. EW Roubos and Dr. T Kozicz
• 2002–2006    Doctorate (PhD) Dissertation: “Neurobiology of stress adaptation in the mouse: Roles of corticotropin-releasing factor and urocortin 1”. Department of Cellular Animal Physiology, Radboud University Nijmegen, The Netherlands, with Prof. Dr. E.W. Roubos and Dr. Tams Kozicz and Department of Psychopharmacology, University of Utrecht, the Netherlands, with Prof. Dr. B. Olivier.
• 1999-2001    Master (M.Sc.) (with Honors) M.Sc.Thesis: “The development of a model for absence epilepsy: analysis of the morpho-functional changes in the forebrain of the WAG/Rij rat”. Department of Developmental Biology, University of Turin, Turin, Italy with Prof. Dr. A. Fasolo and Department of Cellular Animal Physiology, Radboud University Nijmegen, with Prof. Dr. E.W. Roubos.
• 1996-1999    Bachelor (B.Sc.) Department of Biology, University of Turin, Italy