Researchers have mapped cell development in the adult human hippocampus and found that brains from people with depression produce new neurons less effectively than those without the condition, Nature reported.
Authors of the study, published in Nature Medicine, analysed post-mortem brain tissue collected from 30 individuals shortly after death. Eleven donors had major depressive disorder, while 19 donors without mental health conditions served as a control group. Scientists used single-nucleus RNA sequencing on nearly 500,000 cells from the hippocampus to capture gene activity snapshots that reveal cell maturity levels.
Donors with clinical depression showed a higher proportion of neural stem cells and a lower proportion of neuroblasts compared with the control group. In typical neurogenesis, neural stem cells turn into intermediate progenitor cells, advance into neuroblasts, and eventually become immature neurons. Maura Boldrini Dupont, a neuroscientist at Columbia University and study co-author, noted that the progression in depressed brains appeared stalled and lagging behind.
Dupont and her colleagues identified several potentially druggable molecular pathways involved in the process, though the research does not establish that disrupted neurogenesis directly causes depression. Amelia Eisch, a neuroscientist at the University of Pennsylvania who was not involved in the study, noted that the work is the first to use single-cell resolution to pinpoint where the process falters.
Gerd Kempermann, a neuroscientist at the German Center for Neurodegenerative Diseases, said the findings provide evidence that adult neurogenesis occurs and that freshly generated neurons serve distinct functions in the brain.
Tissue measurements did not show a lower proportion of immature neurons in donors with major depressive disorder compared with controls. Evgenia Salta, a neuroscientist at the Netherlands Institute for Neuroscience, noted that this specific outcome demonstrates the need for further research into how neurogenesis alters as disease progresses.
