Humans and dolphins: Decline and fall of adult neurogenesis

Pre-clinical research is carried out on animal models, mostly laboratory rodents, with the ultimate aim of translating the acquired knowledge to humans. In the last decades, adult neurogenesis (AN) has been intensively studied since it is viewed as a tool for fostering brain plasticity, possibly repair. Yet, occurrence, location, and rate of AN vary among mammals: the capability for constitutive neuronal production is substantially reduced when comparing small-brained, short living (laboratory rodents) and large-brained, long-living species (humans, dolphins). Several difficulties concerning scarce availability of fresh tissues, technical limits and ethical concerns did contribute in delaying and diverting the achievement of the picture of neurogenic plasticity in large-brained mammals. Some reports appeared in the last few years, starting to shed more light on this issue. Despite technical limits, data from recent studies mostly converge to indicate that neurogenesis is vestigial, or possibly absent, in regions of the adult human brain where in rodents neuronal addition continues into adult life. Analyses carried out in dolphins, mammals devoid of olfaction, but descendant of ancestors provided with olfaction, has shown disappearance of neurogenesis in both neonatal and adult individuals. Heterogeneity in mammalian structural plasticity remains largely underestimated by scientists focusing their research in rodents. Comparative studies are the key to understand the function of AN and the possible translational significance of neuronal replacement in humans. Here, we summarize comparative studies on AN and discuss the evolutionary implications of variations on the recruitment of new neurons in different regions and different species

Osteogenic and Neurogenic Stem Cells in Their Own Place: Unraveling Differences and Similarities Between Niches

Although therapeutic use of stem cells (SCs) is already available in some tissues (cornea, blood, and skin), in most organs we are far from reaching the translational goal of regenerative medicine. In the nervous system, due to intrinsic features which make it refractory to regeneration/repair, it is very hard to obtain functionally integrated regenerative outcomes, even starting from its own SCs (the neural stem cells; NSCs). Besides NSCs, mesenchymal stem cells (MSCs) have also been proposed for therapeutic purposes in neurological diseases. Yet, direct (regenerative) and indirect (bystander) effects are often confused, as are MSCs and bone marrow-derived (stromal, osteogenic) stem cells (BMSCs), whose plasticity is actually overestimated (i.e., trans-differentiation along non-mesodermal lineages, including neural fates). In order to better understand failure in the "regenerative" use of SCs for neurological disorders, it could be helpful to understand how NSCs and BMSCs have adapted to their respective organ niches. In this perspective, here the adult osteogenic and neurogenic niches are considered and compared within their in vivo environment

Humans and Dolphins: Decline and Fall of Adult Neurogenesis

Pre-clinical research is carried out on animal models, mostly laboratory rodents, with the ultimate aim of translating the acquired knowledge to humans. In the last decades, adult neurogenesis (AN) has been intensively studied since it is viewed as a tool for fostering brain plasticity, possibly repair. Yet, occurrence, location, and rate of AN vary among mammals: the capability for constitutive neuronal production is substantially reduced when comparing small-brained, short living (laboratory rodents) and large-brained, long-living species (humans, dolphins). Several difficulties concerning scarce availability of fresh tissues, technical limits and ethical concerns did contribute in delaying and diverting the achievement of the picture of neurogenic plasticity in large-brained mammals. Some reports appeared in the last few years, starting to shed more light on this issue. Despite technical limits, data from recent studies mostly converge to indicate that neurogenesis is vestigial, or possibly absent, in regions of the adult human brain where in rodents neuronal addition continues into adult life. Analyses carried out in dolphins, mammals devoid of olfaction, but descendant of ancestors provided with olfaction, has shown disappearance of neurogenesis in both neonatal and adult individuals. Heterogeneity in mammalian structural plasticity remains largely underestimated by scientists focusing their research in rodents. Comparative studies are the key to understand the function of AN and the possible translational significance of neuronal replacement in humans. Here, we summarize comparative studies on AN and discuss the evolutionary implications of variations on the recruitment of new neurons in different regions and different species