Understanding the Real State of Human Adult Hippocampal Neurogenesis From Studies of Rodents and Non-human Primates

Abstract

The concept of adult hippocampal neurogenesis (AHN) has been widely accepted, and a large number of studies have been performed in rodents using modern experimental techniques, which have clarified the nature and developmental processes of adult neural stem/progenitor cells, the functions of AHN, such as memory and learning, and its association with neural diseases. However, a fundamental problem is that it remains unclear as to what extent AHN actually occurs in humans. The answer to this is indispensable when physiological and pathological functions of human AHN are deduced from studies of rodent AHN, but there are controversial data on the extent of human AHN. In this review, studies on AHN performed in rodents and humans will be briefly reviewed, followed by a discussion of the studies in non-human primates. Then, how data of rodent and non-human primate AHN should be applied for understanding human AHN will be discussed.

3D Image Analysis of the Complete Ventricular-Subventricular Zone Stem Cell Niche Reveals Significant Vasculature Changes and Progenitor Deficits in Males Versus Females with Aging

“…Therefore, age-dependent changes in these local sources deserve further investigation, as do changes in the various receptors to progesterone, androgens, and estrogens that exhibit differential expression on brain cell subtypes (Contreras-Zárate and Cittelly, 2020). It will also be worthwhile exploring whether similar sexual dimorphism of the periventricular region or other zones that harbor NPCs in humans (Nicaise et al, 2020;Seki, 2020), occurs with aging, such as altered vascular structure and abnormal progenitor proliferation (Matarredona and Pastor, 2019), as these could contribute to different courses in age-related brain diseases in men and women.…”

Brain Plasticity in Humans and Model Systems: Advances, Challenges, and Future Directions

“…Finally, the outcome of reactive neurogenesis and cell reprogramming should not be confused with another process called "dematuration", which is associated with the re-expression of molecules associated with immaturity (e.g., DCX and calretinin), and which has been described to occur in old individuals as a consequence of inflammation, neuronal hyperexcitation, and drug administration [98]. Dematuration is a process in which "mature neurons dedifferentiate to a pseudo-immature status and re-express the molecular markers of neural progenitor cells and immature neurons" [98,99], and is different from de-differentiation. In summary, the complex, heterogeneous issue of brain maturation, as a prerequisite for plasticity, is important in normal CNS postnatal development, influenced by the environment [28], and potentially fundamental in preventing or curing a wide range of neurological disorders.…”

“…These data are consistent with the prediction determined by Sorrells et al [33,78] who report that the relative number of newly born neurons decline to hard-to-detect levels during childhood in humans. It is clear from studies across humans and model systems that some immature neurons (DCX+ neurons) might persist in adulthood because of the availability of markers to capture such processes [16,99,105]; see below. Olfactory and hippocampal adult neurogenesis occur with different rates and time courses in humans.…”

Involvement of Thyroid Hormones in Brain Development and Cancer

“…On the other hand, as long as it concerns adult neurogenesis, while there is a general agreement on adult hippocampal neurogenesis (AHN) in the dentate gyrus of rodents, data available for the human brain are somehow discrepant, and the generation of new neurons throughout life still remains to be definitively determined [ 228 , 229 , 230 , 231 , 232 ].…”