Theorizing that Adult Neurogenesis is Linked to Olfactory Function

Neurogenesis is the production and integration of new neurons into neural networks in the brain. Along with synaptic plasticity, it determines the ability of the brain to recover from damage. There is some controversy over the degree to which it occurs in adult humans; the consensus is that it does, but the vast majority of research on this topic has been carried out in mice, not humans. If there is little or no natural neurogenesis in the adult human brain, a situation quite different from that of mice, then the prospects diminish for the development of therapies to hold back aging that work by increasing neurogenesis. This is an important topic in the field of regenenerative research.

The open access paper noted here offers an interesting hypothesis: that humans and a range of other larger-brained mammals exhibit lesser (or possibly absent) adult neurogenesis because they have lost olfactory function over evolutionary time. We should consider adult neurogenesis to be a co-evolved feature of large and capable olfactory systems in the brain, and we do not have a large and capable olfactory system. Mice do. This is a tenuous hypothesis, in need of considerable support, but it is worth thinking over for a few moments.

The majority of mammals show adult hippocampal neurogenesis to some extent, with exceptions in dolphins, humans, and some bats. Neurogenesis seems to be under selective pressure. Under an evolutionary profile, humans have it during the youngest ages that likely had the greatest phylogenetic importance in the past. Open questions about adult human neurogenesis include: (i) are low levels of neurogenesis functionally relevant? (ii) are there vestigial/quiescent remnants of stem cell niches and can these be reactivated in some way? Some authors, considering that the new neurons within the dentate gyrus, even a low number, can be highly functional (at least in animal models), argue that "there has been evolution toward neurogenesis-based plasticity rather than away from it". At present, no systematic, fully comparable studies are available on a wide range of mammalian species to support this view.

The most likely explanation for the general reduction of adult neurogenesis in humans when compared to rodents might be related to the reduced importance of specific brain functions linked to survival, replaced by other (higher) cognitive functions. This potential explanation acquires relevance when olfaction/olfactory brain structures, such as subventricular zone (SVZ) neurogenesis, are concerned. Although olfaction in humans is considered more impactful than previously thought (in term of total amount of neurons), the relative size of the olfactory bulb with respect to the whole brain volume (0.01% of the human brain compared to 2% of the mouse brain) and the importance of olfaction for survival are quite reduced when compared to rodents.

Dolphins are large-brained mammals. Among several aspects worthy of a comparative study on neurogenic activity in dolphins, we focused on a unique trait: the absence of olfaction/olfactory brain structures. We recently expressly searched the periventricular region of dolphins for neurogenic processes. The persistence of a vestigial remnant (functionally inactive) of the SVZ neurogenic niche in dolphins strongly suggests that periventricular neurogenesis reduction or disappearance occurs in parallel with reduction or disappearance of olfactory brain structures across evolution.

In conclusion, three features of adult neurogenesis are crucial when considering its translational value: (i) its substantial decrease in humans and other long-living, large-brained mammals; (ii) its decrease with the age of the individuals (in both SVZ and hippocampus); and (iii) a scarce propensity/efficacy for lesion-induced repair in mammals. These constraints seem to strongly depend on evolutionary pathways. Evolution drives the occurrence, rate, and type of plasticity among mammals, and interspecies differences must be taken into account when translating results from mice to humans.