Neurogenesis and the impact of steroid hormones on behaviour

Abstract

It took almost a century to get over the dogma of impossibility of adult neurogenesis. A growing number of researches in the past few decades have brought phenomena of adult neurogenesis into light. Ideas of therapeutic possibilities of neural stem cells in managing brain stroke, traumatic brain and spinal cord injury, as well as growing number of neurodegenerative diseases, represent the basis of huge research projects. After the development of CNS is finished, neurogenesis continues in two regions of the adult brain: sub ventricular zone of lateral ventricles and sub granular zone of dentate gyri of hippocampus. The process of neurogenesis brings two main questions concerning the regulatory mechanism: which factors enhance or suppress it and what is the significance of the process in humans. Brain development is under crucial influence of steroid hormones (effects are mediated through gene interaction or by neuromodulation of ion channel), so their influence on behaviour cannot be neglected. Studies have shown that hormones modulate learning and memory, but the specific roles of each of them should be monitored under a wide context of time, pre-exposition test manipulation, training as well as type of testing. Stress is another important factor in the regulation of adult neurogenesis, but current results highlight the importance of the opposite direction as well and young neurons interaction activity with HPA axis. Neurosteroids (allopregnanolone, dihydroepiandrosterone) are synthesized in the brain, and their concentrations are found higher than in blood of mammals. A number of steroidogenic enzymes (rate limiting enzymes in synthesis from cholesterol) are targeted in the brain, spinal cord and peripheral nervous system. The significance of neurosteroids' existence in brain tissue is explored through experiments of epileptogenesis. Numerous researches are trying to determine whether and how hormone alterations in neuroplasticity and neurogenesis are related to changes in cognition. Progesterone has been shown to improve neurologic outcome in multiple experimental models but it failed to show effect through two phase III clinical trials in patients with traumatic brain injury.