Regulation of neurogenesis in the aging vertebrate brain: role of oxidative stress and neuropsychiatric factors

Neurogenesis persists in the subventricular zone of the lateral ventricles and in the dentate gyrus of the hippocampus of the vertebrate brain throughout adulthood. Though the rate of neurogenesis decreases dramatically with increasing age, neurons continue to be born throughout old age in rodents, primates, and human beings. This decline, however, is not irreversible and may be prevented in part by the action of numerous trophic and other regulatory factors. Among these are FGF-2 and BDNF as well as several psychotrophic factors used in the treatment of neuropsychiatric disorders, including serotonin, lithium, and a number of antidepressants. In addition, exposure to a challenging and complex environment (‘enriched environment’) has been demonstrated to have striking neuroprotective effects. In the context of a link between neurogenesis and neuropsychiatric disorders, we propose one possible mechanism, oxidative stress, through which substances such as alcohol may impair neurogenesis. We also explore the potential functional significance of adult neurogenesis in the hippocampus and consider the evidence suggesting a role in the cognitive functions of learning and memory.