(Patho)physiological regulation of adult hippocampal neurogenesis By seizures, glucocorticoids and microRNAs

This thesis specifically focused on the direct regulation of neural stem cells (NSCs); a crucial process for the generation of new neurons throughout life in the mammalian brain. Mammalian species are constantly exposed to environmental challenges for which adaptation of brain function through e.g. neuronal modulation and plasticity is crucial. Adult hippocampal neurogenesis (AHN) constitutes one of the recent, most intensively studied forms of structural plasticity. It has long been proposed that newborn neurons are needed in certain types of hippocampus-dependent memory functions, and therefore would relate to cognitive capacity of mammalian species. While there is evidence for the involvement of newborn granule cells (GCs) in these functions, a unified theoretical framework for adult neurogenesis has not been reached yet and will likely require more experimental data.
The capacity of the adult hippocampal stem cell pool to generate new neurons while maintaining itself is not indefinite, and this capacity decreases with age. To prevent an early exhaustion of the adult hippocampal stem cell pool, AHN must be tightly regulated and several cell intrinsic and extrinsic signaling pathways have been identified that regulate AHN. Deregulation of AHN is a hallmark of many brain pathologies, including epilepsy, although its exact role in these pathologies remains mostly unclear. Here, we aimed to identify new regulatory pathways of AHN in both health and disease, focusing on epigenetic mechanisms.