HUMAN ADULT HIPPOCAMPAL NEUROGENESIS IS SHAPED BY NEUROPSYCHIATRIC DISORDERS, DEMOGRAPHICS, AND LIFESTYLE-RELATED FACTORS

Adult hippocampal neurogenesis (AHN) regulates hippocampal-dependent functions and is targeted by physiological aging and neurodegenerative conditions. Patients with neuropsychiatric disorders show structural and functional abnormalities in the hippocampus. However, whether AHN impairments underlie these alterations remains unknown. To address this question, we aimed to determine whether major depression (MD), schizophrenia (SCH), and bipolar disorder (BD) compromise the integrity of human AHN and the homeostasis of the dentate gyrus neurogenic niche – a specialized micro-environment in which new neurons grow. Our study examined a cohort of 59 human subjects. Fresh frozen glass-slide-mounted 14µm hippocampal sections were obtained, including tissue from 14 neurologically healthy control subjects and 45 patients (15 per diagnosis group: MD, SCH, and BD). Using immunohistochemistry and confocal microscopy imaging, we conducted an in-depth analysis of hippocampal sections to assess alterations across individual AHN stages in neuropsychiatric disorders. Additionally, we evaluated alterations of the neurogenic niche components including astrocytes, microglia, and blood vessels. Our results show that the initial and intermediate stages of AHN, as well as distinct components of the niche, are selectively affected in these disorders. Demographics and various lifestyle-related factors (such as the consumption of alcohol and drugs of abuse) modulate both AHN and the cells that compose the niche, not only in patients with these disorders but also in neurologically healthy control individuals. These data might be relevant for the design of future therapeutic strategies to prevent or treat mental health disorders.