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

Abstract

Plasticity, and in particular, neurogenesis, is a promising target to treat and prevent a wide variety of diseases (e.g., epilepsy, stroke, dementia). There are different types of plasticity, which vary with age, brain region, and species. These observations stress the importance of defining plasticity along temporal and spatial dimensions. We review recent studies focused on brain plasticity across the lifespan and in different species. One main theme to emerge from this work is that plasticity declines with age but that we have yet to map these different forms of plasticity across species. As part of this effort, we discuss our recent progress aimed to identify corresponding ages across species, and how this information can be used to map temporal variation in plasticity from model systems to humans.

The PSA-NCAM-Positive “Immature” Neurons: An Old Discovery Providing New Vistas on Brain Structural Plasticity

“…At least three main types of structural plasticity are recognized: (i) synaptic plasticity, including formation, elimination, and functional modulation of synaptic contacts [4]; (ii) adult neurogenesis, intended as a lifelong stem cell-driven formation of new neurons [13,24]; (iii) the recently discovered, non-newly generated, "immature" neurons as a form of "neurogenesis without division" (reviewed in [44,45]; see below). Several aspects of these forms of plasticity, including their occurrence, location, extension, and amount, can remarkably vary among mammals at different ages [20]. Current studies reveal that this landscape can be even more complex due to a possible mix/overlapping of neurogenic and non-neurogenic processes, which, in this case, strictly depend on different species and ages [46][47][48].…”

“…Most of all, there is a need for markers to reconstruct the whole life of t cells after their last mitotic division. Finally, we need further knowledge for translati time science to enhance the interpretation of findings from animal model-based stud [20,21]. Based on these facts, a hypothesis has been proposed that immature neuronal markerexpressing neurons in the human dentate gyrus are derived from (1) adult-born neurons with prolonged immature neuronal marker expression, (2) prenatally born immature neuronal marker-expressing neurons, and (3) immature neuronal marker-re-expressing neurons [118].…”

“…Most of all, there is a need for markers to reconstruct the whole life of the cells after their last mitotic division. Finally, we need further knowledge for translating time science to enhance the interpretation of findings from animal model-based studies [20,21].…”

“…Despite the vast amounts of data produced across the years by neurobiological research, many aspects of brain plasticity remain obscure, especially as to whether and how plasticity is an extension of "embryonic features" or "immaturity". In addition, it is more and more evident that brain plasticity can remarkably vary as to its type, location, and extension among mammalian species [16][17][18][19][20]. Currently, it is an open question which types of plasticity, and time courses, are sufficiently conserved between model systems and humans as to be relevant to human health [20,21].…”

“…In addition, it is more and more evident that brain plasticity can remarkably vary as to its type, location, and extension among mammalian species [16][17][18][19][20]. Currently, it is an open question which types of plasticity, and time courses, are sufficiently conserved between model systems and humans as to be relevant to human health [20,21].…”