About me

I am a PhD student in the group of Prof.Dr. Paul J. Lucassen under the supervision of Dr. Carlos P. Fitzsimons at the Center for Neuroscience, University of Amsterdam. My PhD project is entitled: Glucocorticoids and molecular control of adult hippocampal neurogenesis.

Adult hippocampal neurogenesis?

It is now widely accepted that new neurons are born in the adult mammalian brain, a process referred to as adult neurogenesis. Although this takes place in more than one brain region, I am especially interested in the hippocampus for its involvement in disorders such as depression, Alzheimer's and epilepsy. 
Adult hippocampal neurogenesis is a multi-step process that starts with neural stem cells and end with the functional integration of a new neuron roughly one month later. In this time-frame of one month a lot of regulation is occurring, both extrinsic (e.g. stress hormones) and intrinsic (e.g. epigenetic factors such as small non coding RNAs).   
 
Left | Zooming in on adult hippocampal neurogenesis

Glucocorticoids: stress hormones and more

One of my goals is to understand how stressful events contribute to the predisposition to develop stress-related diseases. Within this framework, my research is focused on how stress hormones (glucocorticoids) regulate hippocampal neural stem cells (NSC) and the brains' structural plasticity.
Previous studies from our group have shown that some of the effects of stress on for example NSCs proliferation are reversible in vivo. On the other hand, recent studies have proposed that adult hippocampal neurogenesisprovides a buffer to dampen the effects of stress on behavior. In this view, subsequent repeated, or chronic, stressful episodes would "titrate down" this buffer of neurogenesis, and promote vulnerability to develop stress related disorders over time. Hence, one key question in my PhD research is whether the effects of stress on NSC proliferation are fully reversible?

Above | Glucocorticoids (DEX) regulate neural stem cell proliferation (Ki67) in a dose dependent manner in vitro .

Another central question I have is how neurogenesis is regulated under basal (non stressed) conditions by glucocorticoids, which are also released to act as circadian and ultradian "pacemakers".

Above | Without any known stressor, removing the glucocorticoid receptor from neural stem cells  and their progeny in vivo, alters their migration, dendritic arborization and integration 14 days later.

Cell intrinsic regulators of neurogenesis: microRNAs

A recently emerging group of cell intrinsic regulatory "master switches" are the small non coding RNAs, another line of research I'm interested in. Among the small non coding RNAs are microRNA, for which many regulatory functions have been described in neurogenesis.
Left | How different microRNAs affect the different stages of neurogenesis through preventing their target mRNAs from being translated into proteins.

Selection of publications

Knockdown of the glucocorticoid receptor alters functional integration of newborn neurons in the adult hippocampus and impairs fear-motivated behavior.  Fitzsimons CP, van Hooijdonk LWA,  Schouten M , Zalachoras I, Brinks V, Zheng T, Schouten TG, Saaltink DJ, Dijkmans T, Steindler DA, Verhaagen J, Verbeek FJ, Lucassen PJ, de Kloet ER, Meijer OC, Karst H, Joels M, Oitzl MS and Vreugdenhil E.  Mol Psychiatry.  2012 Aug 28. doi: 10.1038/mp.2012.123  
  

New Neurons in Aging Brains: Molecular Control by Small Non-Coding RNAs.  Schouten M , Buijink MR, Lucassen PJ, Fitzsimons CP. Front Neurosci.   2012;6:25

Early-life stress mediated modulation of adult neurogenesis and behavior. Korosi A, Naninck EF, Oomen CA,  Schouten M , Krugers H, Fitzsimons C, Lucassen PJ. 
 Behav Brain Res.  2012 Feb 14;227(2):400-9

Comparison of AAV Serotypes for GeneDeliveryto Dopaminergic Neurons in the Substantia Nigra. Korecka J,  Schouten M , Eggers R, Ulusoy A, Bossers K, Verhaagen J. Viral Gene Therapy, Dr. Ke Xu (Ed.), ISBN: 978-953-307-539-6, InTech, Available from: http://www.intechopen.com/books/viral-gene-therapy/comparison-of-aav-serotypes-for-gene-delivery-to-dopaminergic-neurons-in-the-substantia-nigra

Selection of meetings

• 2012 Dutch Endo-Neuro-Psycho meeting

Proteomics analysis of kainic acid-induced changes in the mouse hippocampus reveals microRNAs as regulators of neural stem cell apoptosis. M. Schouten, S.A. Fratantoni, C.J.Y. Hubens, S.R. Piersma, T.V. Pham, E. Vreugdenhil, P.J. Lucassen, C.R. Jimenez, C.P. Fitzsimons

Modular proteins as innovative non-viral vectors for gene therapy of the brain. J. Domingo-Espín, M. Schouten, R.R.C.E. Schreurs, A. Villaverde, E. Vazquez, N. Ferrer-Miralles, C.P. Fitzsimons

Targeting the neurogenic cells of the adult mouse hippocampus using modular protein-only particles. R.R.C.E. Schreurs, J. Domingo-Éspin, M. Schouten, C.P. Fitzsimons

• 2012 FENS Satellite: Regulation of adult neurogenesis: from epigenetics to behavior

Changes in the cyclic pattern of glucocorticoid exposure affect the progression of adult hippocampal neurogenesis. Marijn Schouten, R. Angela Sarabdjitsingh, Paul J. Lucassen, Onno C. Meijer and Carlos P. Fitzsimons

• 2012 FENS

Proteomics analysis ofkainic acid-induced changes in the mouse hippocampus reveals microRNAs as regulators of neural stem cell apoptosis. M.  Schouten, S.A. Fratantoni, C.J.Y. Hubens, S.R. Piersma, T.V. Pham, E. Vreugdenhil, P.J. Lucassen, C.R. Jimenez, C.P. Fitzsimons

• No ancillary activities