Investigating cell turnover in the healthy and diseased adult human brain

Sammanfattning: For decades it was thought that cells that lost in the human central nervous system because of ageing or disease – different from other cell tissues – cannot be replaced and that in humans all neurons are generated during prenatal development. However, over the last 20 years, it became obvious that there is a certain level of adult neurogenesis in most mammals that mainly occurs in the dentate gyrus and the subventricular zone. Whether or not findings from animal studies also hold true in humans was difficult to study as direct evidence – as obtained in animals from genomic labeling using for instance nucleosides like BrdU – was not feasible in humans because of ethical considerations. The establishment of the so-called radiocarbon technique, a method taking advantage of the above-ground nuclear bomb tests during the Cold War to retrospectively birth date cells by determination of the 12C/14C ratio in genomic DNA – allowed to investigate the age and the turnover dynamics of cells in various human tissues. Applying this technique we here (i) studied whether there is adult neurogenesis in the healthy human brain, specifically within the hippocampus, (ii) studied whether there is adult neurogenesis in the diseased human brain, specifically in response to cortical stroke, and (iii) investigated the age and growth dynamics of brain tumors, specifically benign meningiomas. In essence we demonstrate (i) that there is a lifelong adult neurogenesis within the human hippocampus and provide an integrated model of hippocampal cell turnover dynamics, (ii) that there is no significant induction of cortical neurogenesis following ischemic cortical stroke in humans, and (iii) that the age of benign meningiomas is significantly older than that of more malignant brain tumors. The clinical implications of these findings are discussed and research projects for future studies identified.