AMSTERDAM, The Netherlands, 2 December 2025 -- In a revelatory Genomic Press Interview published today in Brain Medicine, Dr. Paul Lucassen, full professor at the University of Amsterdam and leader of the Brain Plasticity group, shares his scientific journey that helped transform our understanding of how adult brains adapt to challenge and change. His research, spanning topics like apoptosis, neurogenesis, (early life) stress, rodent work, human brain tissue and diseases like depression and dementia, carries implications for those affected by these disorders globally.
From Dementia Bedside to Neurogenesis Discovery
The spark for Dr. Lucassen's career came from an unexpected source: watching an uncle gradually succumb to dementia. "That unfortunate sequence of events piqued my interest in the brain," he recalls. What followed was doctoral research with Dick Swaab at the Netherlands Institute for Neuroscience, investigating a deceptively simple hypothesis.
"I did my PhD with Dick Swaab on the hypothesis that, similar to muscle, activation and 'training' of brain cells is good for them and helps them withstand the deleterious consequences of aging and dementia, a concept paraphrased as 'use it or lose it'," Dr. Lucassen explains. Those years proved formative, involving animal studies and work on human brain material including participation in the nightly autopsies of the Netherlands Brain Bank in Amsterdam. The question of whether neurons could be protected through activity would shape everything that followed.
A pivotal moment arrived during his postdoctoral work on stress and depression. The prevailing theory held that chronic stress could kill hippocampal neurons through glucocorticoid toxicity. But the evidence refused to cooperate. "We could not find much support for it," Dr. Lucassen admits. The realization that hippocampal shrinkage after stress could normalize with recovery suggested something else entirely: perhaps also changes in cell birth, not just cell death, were involved.
A Flight to London That Changed Everything
Learning almost too late about a talk by Rusty Gage on adult neurogenesis, Dr. Lucassen booked a flight and found himself in London the next day. "It completely blew me away," he recounts. 'The discovery that stem cells continue producing new neurons in adult brains represented a paradigm shift for me'. He returned to Amsterdam determined to abandon his cell death research and pursue (adult) cell birth instead.
With colleague Marian Joels and their then first PhD student Vivi Heine, who has since become a professor of stem cell biology, the team began investigating adult neurogenesis in relation to stress, depression, Alzheimer's disease and aging. This work eventually led to the Eurogenesis consortium, connecting researchers like Gerd Kempermann, Nora Abrous, Georg Kuhn, Henriette van Praag, Sebastian Jessberger, Alejandro Schinder, Nico Toni and others. With Liesbeth Reneman, Anouk Schrantee and Mirjana Maletic-Savetic, he works on detecting neurogenesis in vivo, and another topic, as discussed with Evgenia Salta in Cell Stem Cell in 2023, is whether factors that promote neurogenesis can offer protection against neurodegenerative conditions, like Alzheimer's.
