Newborn neurons (white) in the adult rodent hippocampus (blue), image courtesy Dr B. Czeh.

General information; research topics

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.

Personal websites:

http://sils.uva.nl/sfpns

• Verwijzing

Selected recent 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.

- Q Wang, J Van Heerikhuize, L Seress, E Aronica, M Joels, DF Swaab, PJ Lucassen. Glucocorticoid receptor expression in the human hippocampus; stability with age. Neurobiol. Aging, 2013 Jun; 34(6):1662-73.

- 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.

- KJ Doorn, A Goudriaan, C Blits-Huizinga, JGJM Bol, AJ Rozemuller, PVJM Hoogland, PJLucassen,  B Drukarch , WDJ van de Berg and A-M van Dam. Increased amoeboid microglia density is associated with neuronal network disintegration in the olfactory bulb of Parkinson’s and Alzheimer’s disease patients. Brain Pathology 2014.

- Marlatt MW, Potter MC, Bayer TA, van Praag H, Lucassen PJ. Prolonged Running, not Fluoxetine Treatment, Increases Neurogenesis, but does not Alter Neuropathology, in the 3xTg Mouse Model of Alzheimer's Disease. Curr Top Behav Neurosci. 2013;15:313-40.

- Kajo van der Marel, Valentine Bouet, Gideon F. Meerhoff, Pieter Schipper, Anne Klomp, Paul J. Lucassen, Judith R. Homberg, Rick M. Dijkhuizen, Liesbeth Reneman. Long-term oral methylphenidate treatment in adolescent and adult rats: differential effects on brain morphology and function. Neuropsychopharmacology, 2014.

- Q. Wang, E.W.E. Verweij, H.J. Krugers, M Joels, D.F. Swaab, P.J. Lucassen. Distribution of the glucocorticoid receptor in the human amygdala; changes in mood disorder patients. Brain Structure and Function, 2014.

- PJ Lucassen, N Sousa, OFX Almeida, G Rajkowska, J Pruessner, DF Swaab and B Czeh. Neuropathology of Stress. Acta Neuropathologica, 2014.

- CP. Fitzsimons, E van Bodegraven, M Schouten, R Lardenoije, K Kompotis, G Kenis, M van den Hurk, MP. Boks, C Biojone, S Joca, HWM. Steinbusch, K Lunnon, PJ Lucassen, D Mastroeni, J Mill, P Coleman, D van den Hove and BPF. Rutten. Epigenetic regulation of adult neural stem cells. Implications for Alzheimer’s disease. Mol Neurodegeneration, 2014. 

- KJ. Doorn, B Drukarch, AM van Dam, and PJ. Lucassen, Hippocampal Proliferation Is Increased in Presymptomatic Parkinson’s Disease and due to Microglia, Neural Plasticity, 2014. 

- K Boekhoorn, V van Dis, E Goedknegt, A Sobel, PJ. Lucassen and CC. Hoogenraad. The microtubule destabilizing protein stathmin controls the transition from dividing neuronal precursors to post-mitotic neurons during adult hippocampal neurogenesis, Dev Neurobiol, 2014 Jun 7. doi: 10.1002/ 

Video link to Paul Lucassen on Adult Neurogenesis (YouTube);

http://www.youtube.com/watch?v=kIzrLD70vEA

• Paul Lucassen on Stem Cells and Neurogenesis

• Publications of PJ Lucassen on PubMed

Publications 2014;

-Bielefeld P, van Vliet EA, Gorter JA, Lucassen PJ, Fitzsimons CP. Different subsets of newborn granule cells: a possible role in epileptogenesis? Eur J Neurosci. 2014 Jan;39(1):1-11. doi: 10.1111/ejn.12387.

-Karlijn J. Doorn, Andrea Goudriaan, Carla Blits-Huizinga, John G.J.M. Bol, Annemieke J. Rozemuller, Piet V.J.M. Hoogland, Paul J. Lucassen,  Benjamin Drukarch , Wilma D.J. van de Berg and Anne-Marie van Dam. Increased Amoeboid Microglial Density in the Olfactory Bulb of Parkinson's and Alzheimer's Patients. Brain Pathology, Volume 24, Issue 2 pp 152-165, 2014.

-A. Klomp, L. Václavů, G. Meerhoff, L. Reneman, P.J. Lucassen. Effects of chronic fluoxetine treatment on neurogenesis and tryptophan hydroxylase expression in adolescent and adult rats. PlosOne, May 14;9(5):e97603. doi: 10.1371/journal.pone.0097603, 2014. 

-Kajo van der Marel, Anne Klomp, Gideon F Meerhoff, Pieter Schipper, Paul J Lucassen, Judith R Homberg, Rick M Dijkhuizen and Liesbeth Reneman. Long-Term Oral Methylphenidate Treatment in Adolescent and Adult Rats: Differential Effects on Brain Morphology and Function. Neuropsychopharmacology 2014, 39 (2): 263-273.

-Q. Wang, E.W.E. Verweij, H.J. Krugers, M Joels, D.F. Swaab, P.J. Lucassen. Distribution of the glucocorticoid receptor in the human amygdala; changes in mood disorder patients. Brain Structure and Function, in press, 2014.

- Paul J. Lucassen, Jens Pruessner, Nuno Sousa, Osborne F.X. Almeida, Anne Marie Van Dam, Grazyna Rajkowska, Dick F. Swaab and Boldizsár Czéh. Neuropathology of Stress. Acta Neuropathol. 2014 Jan;127(1):109-35.

- Hoeijmakers L, Harbich D, Schmid B, Lucassen PJ, Wagner KV, Schmidt MV, Hartmann J. Depletion of FKBP51 in Female Mice Shapes HPA Axis Activity. PloS One. 2014 Apr 23;9(4):e95796.

- Manila Loi, Sylwia Koricka, Paul J. Lucassen, Marian Joels. Age- and sex-dependent effects of early life stress on hippocampal neurogenesis. Frontiers, Special issue on perinatal stress and psychopathology (Eds; N Daskalakis and R Yehuda), Front Endocrinol (Lausanne). 2014 Feb 20;5:13.

- Karlijn J. Doorn, Benjamin Drukarch, Anne-Marie van Dam, and Paul J. Lucassen, Hippocampal Proliferation Is Increased in Presymptomatic Parkinson’s Disease and due to Microglia, Neural Plasticity, vol. 2014, Article ID 959154, 13 pages, 2014. doi:10.1155/2014/959154

- Karin Boekhoorn, Vera van Dis, Erika Goedknegt, André Sobel, Paul J. Lucassen and Casper C. Hoogenraad. The microtubule destabilizing protein stathmin controls the transition from dividing neuronal precursors to post-mitotic neurons during adult hippocampal neurogenesis, Dev Neurobiol, 2014 Jun 7. doi: 10.1002/dneu.22200.

- Michael W. Marlatt, Jan Bauer, Eleonora Aronica, Elise S. van Haastert, Jeroen J.M. Hoozemans, Marian Joels and Paul J Lucassen. Proliferation in the Alzheimer hippocampus is due to microglia, not astroglia, and occurs at sites of amyloid deposition. Neural Plasticity, 2014.

-CP Fitzsimons, Emma van Bodegraven, Marijn Schouten, Roy Lardenoije, Konstantinos Kompotis, Gunter Kenis, Mark van den Hurk, Marco P. Boks, Caroline Biojone, Samia Joca, Harry W.M. Steinbusch, Katie Lunnon, PJ Lucassen, Diego Mastroeni, Jonathan Mill, Paul Coleman, Daniel van den Hove and Bart P.F. Rutten. Epigenetic regulation of adult neural stem cells. Implications for Alzheimer’s disease. Mol Neurodegen, 2014.

- Karlijn J. Doorn, Tim Moors, Benjamin Drukarch, Paul J. Lucassen and Anne-Marie van Dam. Different microglial phenotypes in the substantia nigra and hippocampus of incidental cases and Parkinson patients: a role for TLR-2 in disease progression ? Acta Neuropathologica Communications.2014, 2:90  DOI: 10.1186.

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