A balanced evaluation of the evidence for adult neurogenesis in humans: implication for neuropsychiatric disorders

Abstract

There is a widespread belief that neurogenesis exists in adult human brain, especially in the dentate gyrus, and it is to be maintained and, if possible, augmented with different stimuli including exercise and certain drugs. Here, we examine the evidence for adult human neurogenesis and note important limitations of the methodologies used to study it. A balanced review of the literature and evaluation of the data indicate that adult neurogenesis in human brain is improbable. In fact, in several high-quality recent studies in adult human brain, unlike in adult brains of other species, neurogenesis was not detectable. These findings suggest that the human brain requires a permanent set of neurons to maintain acquired knowledge for decades, which is essential for complex high cognitive functions unique to humans. Thus, stimulation and/or injection of neural stem cells into human brains may not only disrupt brain homeostatic systems, but also disturb normal neuronal circuits. We propose that the focus of research should be the preservation of brain neurons by prevention of damage, not replacement.

Keywords: Adult neurogenesis; Bromodeoxyuridine; DNA repair/methylation; Homeostasis; Memory; Neural stem cells; Neuronal protection.

Figure 1.

(A-E) Comparison of brain sizes and some migratory distances to illustrate the large differences among mouse and macaque monkey at different developmental points. (F) Amount of adult neurogenesis from “more” in fish, salamanders and other reptiles to “substantial” in birds and rodents, to “less” in monkeys and finally to “none, negligible or not detectable” in humans. The capacity for adult neurogenesis seems negatively correlated to the cognitive capacity in the different species so that the less cognitive complexity the more likely adult neurogenesis is present. Rakic (1985) postulated that humans, throughout evolution, lost their capacity to regenerate neurons in exchange for stability in the neural networks so that processes of memory, learning and higher cognitive functions were favored. Scale bars: 1.0 mm (A-C), 4.0 mm in (D). Macaque tissue examples are from MacBrainResource.org.