Re-cycling Paradigms: Cell Cycle Regulation in Adult Hippocampal Neurogenesis and Implications for Depression

Abstract

Since adult neurogenesis became a widely accepted phenomenon, much effort has been put in trying to understand the mechanisms involved in its regulation. In addition, the pathophysiology of several neuropsychiatric disorders, such as depression, has been associated with imbalances in adult hippocampal neurogenesis. These imbalances may ultimately reflect alterations at the cell cycle level, as a common mechanism through which intrinsic and extrinsic stimuli interact with the neurogenic niche properties. Thus, the comprehension of these regulatory mechanisms has become of major importance to disclose novel therapeutic targets. In this review, we first present a comprehensive view on the cell cycle components and mechanisms that were identified in the context of the homeostatic adult hippocampal neurogenic niche. Then, we focus on recent work regarding the cell cycle changes and signaling pathways that are responsible for the neurogenesis imbalances observed in neuropathological conditions, with a particular emphasis on depression.

Mice with ablated adult brain neurogenesis are not impaired in antidepressant response to chronic fluoxetine

“…In conclusion, our studies do not support the role of adult neurogenesis in pharmacological treatment of depression with fluoxetine as well as put in question a strategy to search for novel therapeutic approaches aiming at cell-cycle stimulation and induction of adult neurogenesis (comp. Patricio et al, 2013).…”

Detection and Phenotypic Characterization of Adult Neurogenesis

“…This benefit of labeling endogenous cell-cycle proteins has been applied to normal and pathological states, such as human depression (reviewed in Patricio et al 2013), and may afford researchers a novel approach to understanding the regulation of neurogenesis from a cell-cycle perspective. Another practical advantage of endogenous protein detection is in studies, in which it is not feasible to deliver thymidine analogs, such as in use of wild animal populations and human postmortem tissue.…”

Influence of single and repeated cannabidiol administration on emotional behavior and markers of cell proliferation and neurogenesis in non-stressed mice

“…In the adult mammalian brain, neurogenesis has been shown to occur in at least two different regions: the subventricular zone (SVZ) of the lateral ventricles and subgranular zone (SGZ) of the hippocampal dentate gyrus (DG) (Patrício et al, 2013). Neuroblasts that are born in the SVZ migrate along the rostral migratory stream (RMS), becoming mostly mature γ-aminobutyric acid (GABA)-ergic granule and periglomerular interneurons in the olfactory bulb (Lois and Alvarez-Buylla, 1993;Doetsch et al, 1999).…”