Our main interest is structural plasticity in relation to stress and disease.
In addition to apoptosis, we focus on the regulation of adult neurogenesis and
its relevance for cognition, depression and dementia. Neurogenesis is prominent
particularly during early development, and our primary focus is effects of early
stress on (development of) the hippocampus. This brain structure is very
sensitive to stress hormone action, implicated in learning and memory and
affected in both these disease conditions. The hippocampus is furthermore unique
as it contains stem cells that continue to generate new neurons in adult
animals, including humans, a process called "adult neurogenesis".
Key interest is the functional relevance of adult neurogenesis for brain function. We are interested in whether blockade or normalization of stress effects on neurogenesis in adult life can be beneficial in terms of e.g. recovery from depression. We hypothesize that e.g. stress-inducedreductions in the number of newborn neurons is deterined during early development and will interfere with the role of the hippocampus e.g. in cognition and in negative feedback of the HPA-axis in adult life. We further study how such deficits can be influenced and possibly ameliorated by means of early diet, antidepressant treatment, or physical or cognitively challenging events such as life long learning and exercise.
Selected recent key publications;
- PJ Lucassen, CP Fitzsimons, A Korosi, M Joels, C Belzung and DN Abrous. Stressing new neurons into depression? Mol Psychiatry 2013 18: 396-397.
- C P Fitzsimons, L W A van Hooijdonk, M Schouten, I Zalachoras, V Brinks, T Zheng, T G Schouten, D J Saaltink, T Dijkmans, D A Steindler, J Verhaagen, F J Verbeek, P J Lucassen, E R de Kloet, O C Meijer, H Karst, M Joels, M S Oitzl and E Vreugdenhil. Knockdown of the glucocorticoid receptor alters functional integration of newborn neurons in the adult hippocampus and impairs fear-motivated behavior. Mol Psychiatry 2013 18: 993-1005.
- I Zalachoras, R Houtman, E Atucha, R Devos, AMI Tijssen, P Hu, P Lockey, NA Datson, J Belanoff , PJ Lucassen, M Joëls, ER de Kloet, B Roozendaal, H Hunt, OC Meijer. Differential Targeting of Brain Stress Circuits with a Selective Glucorticoid Receptor Modulator. Proc Natl Acad Sci U S A. 2013 May 7;110(19):7910-5.
- Paul J. Lucassen, Eva F.G. Naninck, Johannes B. van Goudoever, Carlos Fitzsimons, Marian Joels and Aniko Korosi. Perinatal programming of hippocampal structure and function; emerging roles of stress, neurogenesis, epigenetics and early nutrition. Trends in Neuroscience, 2013.
- PJ Lucassen, N Sousa, OFX Almeida, G Rajkowska, J Pruessner, DF Swaab and B Czeh. Neuropathology of Stress. Acta Neuropathologica, 2014.
- A. Schrantee, G.H. Tamminga, C. Bouziane, M.A. Bottelier, E.E. Bron, H.J.M. Mutsaerts, K. Zwinderman, I.R. Groote, S.A.R.B. Rombouts, R.J.L. Lindauer, W. Niessen, S. Klein, B.C. Opmeer, F. Boer, P.J. Lucassen, S.L. Andersen, H.M. Geurts and L. Reneman. A randomized trial on the age-dependency of methylphenidate effects on the human dopamine system. JAMA Psychiatry, 2016; 73(9):955-62.
- SL Lesuis, H Maurin, P Borghgraef, PJ Lucassen, F Van Leuven, HJ Krugers. Positive and negative early life experiences differentially modulate longterm survival and amyloid protein levels in a mouse model of Alzheimer’s disease. Oncotarget. 2016 Jun 1. doi: 10.18632/oncotarget.9776.
- E.F.G. Naninck, J.E. Oosterink, K.Y.Yam, L. de Vries, H. Schierbeek, J.B. van Goudoever, R.N. Verkaik-Schakel, J.A. Plantinga, T. Plosch, P.J. Lucassen and A. Korosi. Early micronutrient supplementation protects against early stress induced cognitive impairments. The FASEB Journal, 2017 Feb;31(2):505-518, DOI 10.1096/fj.201600834R.
- Yam KY, E.F.G. Naninck, M.R. Abbink, S.E. la Fleur, L. Schipper, J.C. van den Beukel, A. Grefhorst, A. Oosting, E.M. van der Beek, P.J. Lucassen, A. Korosi. Exposure to chronic early-life stress lastingly alters the adipose tissue, the leptin system and changes the vulnerability to western-style diet later in life in mice. Psychoneuroendocrinology 77 (2017) 186–195.
- SL Lesuis, S Weggen, S Baches, PJ Lucassen, HJ Krugers. Early life stress accelerates amyloid pathology and cognitive decline in an Alzheimer mouse model, which can be rescued by briefly blocking glucocorticoid receptors at middle age. Transl. Psych. 2018.
- Kempermann G, Gage FH, Aigner L, Song H, Curtis MA, Thuret S, Kuhn HG, Jessberger S, Frankland PW, Cameron HA, Gould E, Hen R, Abrous DN, Toni N, Schinder AF, Zhao X, Lucassen PJ, Frisén J. Human Adult Neurogenesis: Evidence and Remaining Questions. Cell Stem Cell. 2018.
- SL Lesuis, Hoeijmakers L, Korosi A, de Rooij SR, Swaab DF, Kessels HW, Lucassen PJ*, Krugers HJ*. Vulnerability and resilience to Alzheimer's disease: early life conditions modulate neuropathology and determine cognitive reserve. Alzheimers Res Ther. 2018.
- KY Yam, L Schipper, K Reemst, SR Ruigrok, MR Abbink, L Hoeijmakers, EFG Naninck, P Zarekiani, A Oosting, EM Van der Beek, PJ Lucassen, A Korosi. Increasing availability of omega-3 fatty acid in the early life diet prevents the early-life stress induced cognitive impairments without affecting metabolic alterations. The FASEB Journal 2019.
- J Zhao, PJ Lucassen, DF Swaab. 2019. Suicide is a confounder in postmortem studies on depression. Biol. Psych. 2019.
- Schouten M*, Bielefeld P*, Passchier EMJ, Garcia-Corzo L, Gradari S, Jungenitz T, Pons-Espinal M, Gebara E, Martín-Suárez S, Lucassen PJ, de Vries HE, Schwarzacher SW, De Pietri Tonelli D, Toni N, Trejo JL, Mira H, Encinas JM and Fitzsimons CP. Circadian Glucocorticoid Oscillations Preserve a Population of Adult Hippocampal Neural Stem Cells in the Aging Brain. Mol. Psych. 2020.
- PJ Lucassen, N Toni, G Kempermann, J Frisen, FH Gage and DF Swaab. Limits to human neurogenesis - really? Mol.Psych. 2020.
- Pu Hu, Isabella Maita, Christopher Kwok, Edward Gu, Mark Gergues, Ji Liu, Mimi Phan, Zhiping Pang, Dick F. Swaab, Paul J. Lucassen, Troy A. Roepke, Benjamin A. Samuels. Chronic Stress Induces Anxiety-Associated Negative Valence Behavior by Activating a Corticotropin-Releasing Hormone-Related Molecular Signature in the Oval Bed Nucleus of the Stria Terminalis. J. Neurosci. 40 (12): 2519-2537, 2020.
- Paul J Lucassen, Carlos P. Fitzsimons, Evgenia Salta and Mirjana Maletic-Savatic. Adult neurogenesis - human after all (again)-; classic, optimized and future approaches. Behav. Brain Res., 381 (2020) 112458.
- MR Abbink*, JM Kotah*, L Hoeijmakers, A Mak, G Yvon-Durocher, B van der Gaag, PJ Lucassen, A Korosi. Characterization of astrocytes throughout life in wildtype and APP/PS1 mice after early-life stress exposure. J. NeuroInflam., 2020; 17(1): 91.
- Pu Hu, AM Van Dam, Yu Wang, Paul J. Lucassen, Jiang-Ning Zhou. Retinoic Acid and Depressive Disorders: Evidence and Possible Neurobiological Mechanisms. Neuroscience and Biobehavioral Reviews 112 (2020) 376–391.
- Pascal Bielefeld, Maralinde R. Abbink, Anna R. Davidson, Niels Reijner, Oihane Abiega, Paul J. Lucassen, Aniko Korosi & Carlos P. Fitzsimons (2021): Early life stress decreases cell proliferation and the number of putative adult neural stem cells in the adult hypothalamus. Stress, p.1-15. DOI: 10.1080/10253890.2021.1879787, 2021.
1. Invited Lecture "Structural plasticity in relation to (early) stress, nutrition and depression." Host; Dr. S. Schwarzacher, Dept Klinische NeuroAnatomie, Goethe Universitat, Frankfurt am Main, Germany, 15 Jan 2015.
2. Lecture; 'Trends in Alzheimer's disease research, a personal perspective' at the ISAO Meet and Greet meeting, Jaarbeurs Utrecht, 28 Jan 2015.
3. Invited Lecture "Effects of early life stress and nutrition on adult hippocampal plasticity and function" at MRC Social, Genetic and Developmental Psychiatry Centre (host; Dr Geoff Bird), Institute of Psychiatry, King's College London, United Kingdom, 16 Feb 2015.
4. Lecture 'Plasticity in relation to stress and neurogenesis'. Host; Dr Sandrine Thuret, King's College London, United Kingdom, Febr 17th 2015.
5. Invited Lecture 'Structural plasticity in relation to (early) stress, depression and dementia', at the Department of Fundamental Neurosciences, University of Lausanne (host; Dr. N. Toni), Lausanne, Switzerland, 4th march 2015.
6. Invited lecture 'Hippocampal plasticity in relation to early stress, nutrition and depression', at the Department of Anatomy, ETH (hosts; Dr I Amrein, M Van Dijk), Zurich, Switzerland, 4th March 2015.
7. Invited Lecture "Structural plasticity in relation to (early) stress and depression", at the session on "Structural dynamics of adult neurogenesis" at the 17th International Neuroscience Winter Conference (host; Dr. S. Schwarzarcher), Solden, Switzerland, 10 April 2015.
8. Lecture "Structural plasticity, (early) stress, antidepressants and major depression", at the minisymposium on the occasion of the visit of Dr Snezana Milanovic at the AMC, Amsterdam, 28 may 2015.
9. Invited Lecture 'Application of MRS as tool to measure adult neurogenesis in the live human brain', ABC conference, Theater De Brakke Grond, Amsterdam, 1 Juni 2015.
10. Invited lecture 'Science matters; stress & stem cells', at the Biomedical Symposium Radboud Universiteit Nijmegen, 1 juli 2015.
11. Invited lecture "Hippocampal plasticity in relation to (early) stress, nutrition and depression', at the Adult Neurogenesis meeting, Provence, France, 17 Sept 2015.
12. ECNP supported, plenary lecture at the 8th Simposium Psiquiatria de Braga; 'Structural plasticity in relation to early stress, nutrition and depression' at the University of Minho, Braga, Portugal, Oct 1st 2015.
13. Invited lecture’ ‘'Hippocampal plasticity in relation to early stress, nutrition and depression’ at the symposium on PTSD in Bristol, UK, hosts; Prof.Dr. Hans Reul, Prof.Dr. Astrid Linthorst, 16/17 November 2015.
14. Invited Plenary Lecture "Nieuwe cellen in het volwassen brein; stamcellen en sport" (laymen talk in Dutch) at the Opening Symposium of the "Exercise and the brain" week (supported by the Cruyff foundation) at the Amstelveen College, Amstelveen The Netherlands, 15 Dec 2015.
15. Invited lecture 'Plasticity changes in relation to (early) stress, depression and dementia, at the Danish Academy, Aarhus University, Aarhus, Denmark, 14 jan 2016.
16. Invited lecture 'Hippocampal plasticity in relation to early stress, nutrition and depression", at the 2016 IBRO Workshop, organized by the Hungarian Academy of Sciences, opening lecture of the symposium “Behavioral, Endocrine and Neuropathological Consequences of Stressful Life Events”. Budapest, Hungary, January 22nd, 2016.
17. Invited Plenary lecture 'Ins and outs of Adult Neurogenesis', at the 5th Biennial ICCTF Meeting, Netherlands Cancer Institute Amsterdam, 15th March 2016 (host; Dr. S. Schagen).
18. Invited participant/discussant for the Round Table Expert meeting on Early Life Stress, at the 'Neurobiology of Stress' conference, 12-14 april in Newport Beach, Irvine, USA (host; Prof.Dr. T. Baram).
19. Invited lecture 'Structural plasticity and neurogenesis in relation to (early) stress, depression and dementia', Department of Neuroscience, Universitat de Valencia, Valencia, Spain, April 25th 2016 (host; Dr. J. Nacher).
20. Invited Plenary Lecture "New neurons in adult brains; an emerging substrate for brain plasticity programmed during early life", at the Spring conference on 'Neuroplasticity & Cognitive Reserve' of the Dutch Association for NeuroPsychology, 13 may 2016, (host; Prof.Dr. B. Schmand), Muntgebouw Utrecht, the Netherlands.
21. Invited 'University of Amsterdam' lecture (in Dutch); 'Nieuwe zenuwcellen voor het volwassen brein', at the Universiteitsdag, Oudemanhuispoort, June 4th 2016, Amsterdam.
22. Invited talk 'Early stress and neurogenesis; the importance of nutritional programming for later cognition', at the 3rd EUROGENESIS meeting, July 12-15th 2016, Bordeaux, France.
23. Invited talk "(Early) stress effects on neurogenesis and plasticity", at the meeting of the British Psychiatry Association (BAP), Brighton UK, 17-20 July 2016.
24. Invited lecture; "Hippocampal plasticity, (early) stress and depression" at the ISPNE meeting in Miami, USA. 12 Sept 2016.
25. Invited Keynote speaker on 'Neurogenesis and Alzheimer", University Maastricht, 2 Dec 2016.
26. Invited Lecture "Structural hippocampal plasticity and neurogenesis in relation to dementia", at the Alzheimer Center of the VUMC Amsterdam, hosts; PJ Visser, P Scheltens, W van der Flier, 20 Jan 2017.
27. Lecture 'An overview of Alzheimer research; the state of the affairs (in Dutch)", at the Netherlands Institute for Brain Research NIN, 7 Feb 2017.
28. Invited Lecture 'Structural plasticity in relation to depression and dementia', at the Department of Neurobiology Research, Institute of Molecular Medicine, University of Southern Denmark (host; Prof. Dr. B. Finsen), Odense, Denmark, 9 March 2017.
29. Invited lecture on 'Regulation of neurogenesis by stress and antidepressants' at the Varna meeting on 'Adult primate neurogenesis', Varna, Bulgaria, 20 may 2017.
30. Invited Lecture on 'Our brain under stress (in Dutch)', at the Pawlik Congres – 'Presteren onder Druk', georganiseerd door Pawlik Consultants, Dauphine, Amsterdam, 30 may 2017.
31. Moderator/chair/introductory talk of the session on 'Exercise and psychiatric disease; should patients take the challenge?' at the ECNP meeting in Paris, France, Sept 2017.
32. Invited Lecture ‘New neurons in, and for, adult brains; environmental regulation and functional roles’, within the framework of an ERASMUS exchange program at the Athens University, 24th October 2017.
33. Invited Lecture ‘Stem cells, hippocampal neurogenesis, stress and depression’, at the Dept of Psychiatry, University of Athens (host; Dr M. Panayatocopolou), 25th Oct 2017.
34. Invited laymens talk on ‘Our brain under stress’ (in Dutch), for the crowdfunded project on ‘Stress and the heart’, awarded to Dr A. Schrantee’ at the AMC Amsterdam, 31 Oct 2017.
35. Invited lecture on “Effects of early life stress and nutrition on later brain plasticity and disease vulnerability” at the MQ mental health meeting, London, 2 feb 2018.
36. Invited lecture “Brain plasticity in relation to (early) stress, nutrition and depression’, at the Institute Italiano di Tecnologica in Genova, Italy (host; Dr Davide die Pietri Tonelli), 17 May 2018.
37. Invited Lecture “Neurogenesis, (early) stress and depression’ at the Dutch Neuroscience Meeting, Lunteren, 7th June 2018.
38. Invited lecture ‘Highlights in Dementia’ at the ECNP meeting in Barcelona, 7 Oct 2018.
39. Opening talk at the session ‘Update on Huntington’s and Parkinson’s disease treatment’, at the ECNP meeting, 9th Oct 2018.
40. Lecture on ‘Brain Plasticity’ at the University of Edinburgh, Scotland (host Prof.Dr. J. Seckl), 26th Oct 2018.
41. Invited Lecture; ‘Brain plasticity in relation to early life stress, nutrition and major depression’, on the occasion of the PhD viva of Danka Kozareva at University College Cork, Ireland, hosts Dr. Y Nolan and Prof.Dr. J Cryan, 28th Jan 2019.
42. Invited Lecture; ‘Brain plasticity and neurogenesis in relation to early life stress, nutrition, depression and dementia’, at Neuroscience & Mental Health Research Institute, School of Biosciences, Cardiff University, Cardiff, UK, host Prof.Dr. S Trent, Prof.Dr. J Hall, 14th Feb 2019.
43. Invited Lecture as part of UvA Health Week; ‘What does stress do to your brain?’ UvA, Science Park, 14th May 2019.
44. Invited Lecture ‘Brain Plasticity in relation to (early) stress, nutrition and depression’. Host; Prof.dr. Eleanor Coffey, Turku Centre for Biotechnology, University of Turku and Department of Biosciences, Åbo Akademi University Åbo, Turku, Finland, 17th May 2019.
45. Lecture ‘Brain plasticity in relation to early life stress, nutrition and dementia”, Eurogenesis meeting 14th June 2019, Bordeaux, France.
46. Invited Lecture on; ‘Cognitive reserve and plasticity from a neurobiological perspective; focus on early life’ at the Cognitive Reserve Symposium at the Veranda, host Dr Rik Ossenkoppele and Prof.Dr. W vd Flier, Alzheimer Centrum, Amsterdam, 18 sept 2019.
47. Invited talk on; ‘Brain plasticity in relation to (early life) stress, nutrition and dementia’, host; Prof.Dr. P. Riederer, International WASAD congress, Wuerzburg Germany, 5 Oktober 2019.
48. Invited lecture; ‘Neurobiology of Alzheimer’s disease; recent developments’, (host Dr. I. Philippens) at TNO BPRS Rijswijk, 19 nov 2019.
49. Outreach lecture (in Dutch) in the framework of the ‘Inspiratie week’; ‘Hersenonderzoek in de praktijk', for 3 HV students, Montessori Scholengemeenschap Amsterdam, 21 Nov 2019.
50. Outreach Lecture (in Dutch) on 'What is brain research about these days?', for 4 VWO students at the Herman Wesselink College in Amstelveen, 18 Dec 2019.