Epigenetic (de)regulation of adult hippocampal neurogenesis: implications for depression

Here, we outline some of the major epigenetic mechanisms contributing to the regulation of hippocampal neurogenesis and discuss several lines of evidence supporting their involvement on the development of imbalances in the neurogenic process, often correlated to behavioural and cognitive deficits commonly observed in major depressive disorder.The beauty of research is that it ultimately defeats all established dogmas, even though some take very long to fall. Cajal's decree concerning the immutability of the central nervous system (CNS) has been reviewed and updated during the last decades, due to mounting evidence that substantiates the regenerative potential and plasticity of the CNS. Despite the initial reluctance manifested towards the first reports of post-natal neurogenesis, it is now well established that neurogenesis, a process that comprises the generation, differentiation and integration of new neurons in the preexisting brain neuronal networks, occurs in the adult brain, prevailing throughout life in specific brain areas, where neurons are persistently generated [1,2]. Such spatially defined brain regions where neurogenesis occurs display a permissive microenvironment for the maintenance and differentiation of neural stem cells and to their proliferation. Currently, two neurogenic brain regions are broadly recognized in the mammalian adult brain: the subgranular zone (SGZ) of the hippocampal dentate gyrus (DG) and the subependymal zone (SEZ) in the lateral ventricles.In the hippocampal formation, the precursor cell population resides throughout the SGZ, with specific gradients [3]. After being generated in the SGZ, newly-born cells become committed to a neuronal lineage and migrate into the granule cell layer (GCL), where they mature to become excitatory glutamatergic granule neurons [4,5]. In the SEZ the precursor cells are mostly found in the anterior segment of the walls of the lateral ventricles. Here, newly-born precursor cells generate neuroblasts th