Neurogenesis in the Striatum of the Adult Human Brain

Ernst, Aurélie; Alkass, Kanar; Bernard, Samuel; Salehpour, Mehran; Perl, Shira; Tisdale, John F.; Possnert, Göran; Druid, Henrik; Frisén, Jonas

doi:10.1016/j.cell.2014.01.044

Cited by 805 publications

(764 citation statements)

References 55 publications

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“…In the rodent brain, neuroblasts from the SVZ migrate to the olfactory bulb [52,103]. In the human brain, this migration to the olfactory bulb may be reduced, and neuroblasts may migrate into the basal ganglia [104]. Stroke signals to the SVZ, principally to transit amplifying cells, which proliferate, and to neuroblasts, which migrate to areas of damage.…”

Section: Tissue Regeneration After Strokementioning

confidence: 99%

The 3 Rs of Stroke Biology: Radial, Relayed, and Regenerative

Carmichael

2016

Neurotherapeutics

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Stroke not only causes initial cell death, but also a limited process of repair and recovery. As an overall biological process, stroke has been most often considered from the perspective of early phases of ischemia, how these inter-relate and lead to expansion of the infarct. However, just as the biology of later stages of stroke becomes better understood, the clinical realities of stroke indicate that it is now more a chronic disease than an acute killer. As an overall biological process, it is now more important to understand how early cell death leads to the later, limited recovery so as develop an integrative view of acute to chronic stroke. This progression from death to repair involves sequential stages of primary cell death, secondary injury events, reactive tissue progenitor responses, and formation of new neuronal circuits. This progression is radial: from the tissue that suffers the infarct secondary injury signals, including free radicals and inflammatory cytokines, radiate out from the stroke core to trigger later regenerative events. Injury and repair processes occur not just in the local stroke site, but are also triggered in the connected networks of neurons that had existed in the stroke center: damage signals are relayed throughout a brain network. From these relayed, distributed damage signals, reactive astrocytosis, inflammatory processes, and the formation of new connections occur in distant brain areas. In short, emerging data in stroke cell death studies and the development of the field of stroke neural repair now indicate a continuum in time and in space of progressive events that can be considered as the 3 Rs of stroke biology: radial, relayed, and regenerative.

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Section: Tissue Regeneration After Strokementioning

confidence: 99%

The 3 Rs of Stroke Biology: Radial, Relayed, and Regenerative

Carmichael

2016

Neurotherapeutics

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“…These neuroblasts are generated from clusters of proliferating cells that express the astroglial marker brain lipid-binding protein (BLBP), and about 1/6 of surviving cells differentiate into calretinin-positive striatal interneurons. Using an approach based on the carbon-14 ( 14 C) assay to label cells and identify their age in humans, it was recently proposed that local neurogenesis does occur within the human striatum (Ernst et al 2014). Still in rabbits, the combination of cell proliferation markers, detected at different postinjection survival times, with DCX and PSA-NCAM staining revealed a parenchymal genesis of Pax2 þ interneurons in the cerebellar cortex, resulting from further proliferation of cells of neuroepithelial origin ).…”

Section: Parenchymal Neurogenesismentioning

confidence: 99%

Noncanonical Sites of Adult Neurogenesis in the Mammalian Brain

Feliciano

Bordey

Bonfanti

2015

Cold Spring Harb Perspect Biol

106

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Two decades after the discovery that neural stem cells (NSCs) populate some regions of the mammalian central nervous system (CNS), deep knowledge has been accumulated on their capacity to generate new neurons in the adult brain. This constitutive adult neurogenesis occurs throughout life primarily within remnants of the embryonic germinal layers known as "neurogenic sites." Nevertheless, some processes of neurogliogenesis also occur in the CNS parenchyma commonly considered as "nonneurogenic." This "noncanonical" cell genesis has been the object of many claims, some of which turned out to be not true. Indeed, it is often an "incomplete" process as to its final outcome, heterogeneous by several measures, including regional location, progenitor identity, and fate of the progeny. These aspects also strictly depend on the animal species, suggesting that persistent neurogenic processes have uniquely adapted to the brain anatomy of different mammals. Whereas some examples of noncanonical neurogenesis are strictly parenchymal, others also show stem cell niche-like features and a strong link with the ventricular cavities. This work will review results obtained in a research field that expanded from classic neurogenesis studies involving a variety of areas of the CNS outside of the subventricular zone (SVZ) and subgranular zone (SGZ). It will be highlighted how knowledge concerning noncanonical neurogenic areas is still incomplete owing to its regional and species-specific heterogeneity, and to objective difficulties still hampering its full identification and characterization.

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“…Indeed, the recent observation that humans experience lifelong neurogenesis of a select population of striatal calretinin-positive interneurons is intriguing from a theoretical perspective (Ernst et al 2014); however, the computational function of these interneurons is not well understood even without considering their neurogenic nature. However, based on the discussion above, one possibility is that the striatum (as opposed to the OB) is tasked with a greater computational burden in humans.…”

Section: A Unifying View Of "Why Neurogenesis?"mentioning

confidence: 99%

“…This review will take a slightly different approach, looking at the relationship of neurogenesis to the equivalent nonneurogenic biological system at different scales, and will focus primarily on neurogenesis within the DG with some discussion of the OB. Likewise, adult neurogenesis in the human striatum will receive only a cursory mention, largely because of the fact that the recency of its discovery (Ernst et al 2014) has not yet motivated substantial theoretical work, a fact that will surely change in the future. However, first, it is useful to describe what the value of a new neuron is within the context of abstract neural networks, in general, and then progress to the biological systems in which the specific details of adult neurogenesis interact with the existing network.…”

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confidence: 99%

Computational Modeling of Adult Neurogenesis

Aimone¹

2016

Cold Spring Harb Perspect Biol

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The restriction of adult neurogenesis to only a handful of regions of the brain is suggestive of some shared requirement for this dramatic form of structural plasticity. However, a common driver across neurogenic regions has not yet been identified. Computational studies have been invaluable in providing insight into the functional role of new neurons; however, researchers have typically focused on specific scales ranging from abstract neural networks to specific neural systems, most commonly the dentate gyrus area of the hippocampus. These studies have yielded a number of diverse potential functions for new neurons, ranging from an impact on pattern separation to the incorporation of time into episodic memories to enabling the forgetting of old information. This review will summarize these past computational efforts and discuss whether these proposed theoretical functions can be unified into a common rationale for why neurogenesis is required in these unique neural circuits.T he importance of neurogenesis will be ultimately tied to its impact on the computational function of the overall circuit within which it resides. Notably, the two mammalian regions where neurogenesis is typically studied, the olfactory bulb (OB) and the dentate gyrus (DG) region of the hippocampus, have considerably different functions. The OB is a primary sensory region, essentially the equivalent of the processing layers of the retina, providing an initial transformation of raw olfactory inputs to the brain. In contrast, the hippocampus is one of the deepest structures in the brain, residing many layers away from sensory inputs and vital for episodic memory formation.Interestingly, as noted throughout this collection, although OB and DG neurogenesis share some similarities, there are sufficient differences to make it difficult to generalize across the two systems, not the least of which is the recent observation that humans likely lack OB neurogenesis. This is somewhat supported by a comparative perspective. As with mammals, neurogenesis in birds is limited to several structures with certain species, including neurogenesis in well-studied birdsong regions. Vertebrates with arguably less advanced nervous systems, such as reptiles and fish, have more widespread neurogenesis, suggesting that broad evolutionary pressures to attenuate neurogenesis in other areas of the brain led to the relative isolation of the OB and hippocampus as opposed to an evolutionary gain-of-function process common to the OB and DG. This subtle distinction has implications on how far one can hope for a shared function between these areas and, for this reason, it is not surprising that most computational studies investigating

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Neurogenesis in the Striatum of the Adult Human Brain

Cited by 805 publications

References 55 publications

The 3 Rs of Stroke Biology: Radial, Relayed, and Regenerative

The 3 Rs of Stroke Biology: Radial, Relayed, and Regenerative

Noncanonical Sites of Adult Neurogenesis in the Mammalian Brain

Computational Modeling of Adult Neurogenesis

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