Postnatal Neurogenesis : Its Mechanisms and Significance as a Potential Target for Therapeutics and Intervention for Psychiatric Diseases

Abstract

Neurogenesis occurs dramatically in embryonic stages and continues throughout life in certain brain regions including the hippocampus. Postnatal neurogenesis can be influenced by environmental factors ; neurogenesis is increased by voluntary exercise and reduced by stress in animal models. Various molecules such as intrinsic transcription factors and extrinsic growth factors, cytokines, fatty acids, and nucleic acids are involved in neurogenesis. We have noticed in rodent models that decrease in hippocampal neurogenesis can be a cause for impaired sensorimotor gating, an endophenotype for schizophrenia, scored by prepulse inhibition test. We were able to prove in mice that decreasing neurogenesis by administration of anti-proliferative drug during the critical adolescent stage can induce sensorimotor gating impairment, anxiety, and hyperactivity. We could rescue these phenotypes by introducing enriched environment (i.e., raising multiple mice in a large cage equipped with a running wheel and toys etc.) during the period including the critical stage, whereas we could only rescue hyperactivity if we introduced the enriched environment excluding the critical stage. We consider that neurogenesis can be a potential target for therapeutics and intervention for psychiatric diseases. Better elucidation of neurogenesis, as well as related gliogenesis (more precisely, proliferation and differentiation of oligodendrocyte precursor cells), can lead to our understanding resilience against mental illness in future.