A balanced evaluation of the evidence for adult neurogenesis in humans: implication for neuropsychiatric disorders

Duque, Alvaro; Spector, Reynold

doi:10.1007/s00429-019-01917-6

Cited by 42 publications

(31 citation statements)

References 114 publications

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“…An alternative approach was suggested to be to complement the treatment in neuronal compartments with increasing the production of new neurons to provide resilience and strength to the diseased circuitry (Choi et al, 2018;Moreno-Jimenez et al, 2019;Mu and Gage, 2011;Tincer et al, 2016). Yet, neurogenesis in human brains is quite controversial (Arellano et al, 2018;Cipriani et al, 2018;Dennis et al, 2016;Duque and Spector, 2019;Sorrells et al, 2018). Although many reports documented the presence of adult neurogenesis in human brains (Boldrini et al, 2018;Ernst et al, 2014;Kempermann et al, 2018;Magnusson and Frisen, 2016;Moreno-Jimenez et al, 2019;Spalding et al, 2013), and several studies demonstrated that boosting the neurogenesis might be a viable option for alleviating the cognitive decline (Casse et al, 2018;Choi et al, 2018;Martinez-Canabal, 2014;Papadimitriou et al, 2018;Rodriguez and Verkhratsky, 2011), the potential benefits of neurogenic outcome in AD conditions requires further investigation and critical testing.…”

Section: Introductionmentioning

confidence: 99%

Neuron-glia interaction through Serotonin-BDNF-NGFR axis enables regenerative neurogenesis in Alzheimer’s model of adult zebrafish brain

Bhattarai

Coşacak

Mashkaryan

et al. 2019

Preprint

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It was recently suggested that supplying the brain with new neurons could counteract Alzheimer's disease. This provocative idea requires further testing in experimental models where the molecular basis of disease-induced neuronal regeneration could be investigated. We previously found that zebrafish stimulates neural stem cell (NSC) plasticity and neurogenesis in Alzheimer's disease and could help to understand the mechanisms to be harnessed for develop new neurons in diseased mammalian brains. Here, by performing singlecell transcriptomics, we found that Amyloid toxicity-induced Interleukin-4 induces NSC proliferation and neurogenesis by suppressing the tryptophan metabolism and reducing the production of Serotonin. NSC proliferation was suppressed by Serotonin via downregulation of BDNF-expression in Serotoninresponsive periventricular neurons. BDNF enhances NSC plasticity and neurogenesis via NGFRA/NFkB signaling in zebrafish but not in rodents. Collectively, our results suggest a complex neuron-glia interaction that regulates regenerative neurogenesis after Alzheimer's disease conditions in zebrafish. Key findings-Amyloid-induced Interleukin-4 suppresses Serotonin (5-HT) production in adult zebrafish brain -5-HT affects htr1-expresing neurons and suppresses bdnf expression -BDNF enhances plasticity in neural stem cells via NGFRA/NFkB signaling -BDNF/NGFRA signaling is a neuro-regenerative mechanism in zebrafish but not in mammals.

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Section: Introductionmentioning

confidence: 99%

Neuron-glia interaction through Serotonin-BDNF-NGFR axis enables regenerative neurogenesis in Alzheimer’s model of adult zebrafish brain

Bhattarai

Coşacak

Mashkaryan

et al. 2019

Preprint

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“…peer-reviewed publications, we still do not know if our brain maintains such capability (Duque and Spector, 2019;Petrik and Encinas, 2019;Snyder, 2019). Although we have learned a lot about neural stem cell (NSC) biology and the molecular/cellular mechanisms that sustain neurogenesis in rodents (Bond et al, 2015;Kempermann et al, 2015;Lim and Alvarez-Buylla, 2016), direct analysis of human brain has produced many conflicting results (discussed in Arellano et al, 2018;Kempermann et al, 2018;Paredes et al, 2018;Parolisi et al, 2018;Petrik and Encinas, 2019).…”

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confidence: 99%

“…Subsequently, several studies addressed the issue of AN in a wider range of species, including wild-living and large-brained mammals that displayed a varied repertoire of anatomical and behavioral features, quite different from those of mice (reviewed in Barker et al, 2011;Amrein, 2015;Lipp and Bonfanti, 2016;Paredes et al, 2016;Parolisi et al, 2018). Though still too fragmentary to support exhaustive conclusions about phylogeny (much less function), this landscape of heterogeneity directs us to re-evaluate, discuss and better contextualize the observations obtained in rodents, especially in the perspective of translation to humans (analyzed in Lipp and Bonfanti, 2016;Paredes et al, 2016;Parolisi et al, 2018;Duque and Spector, 2019;Snyder, 2019). Comparative approaches strongly indicate that there is a decrease in the remarkable plastic events that lead to whole cell changes (i.e., AN) with increasing brain size.…”

mentioning

confidence: 99%

“…Why then do some reports claim the existence of AN in humans? Several scientists in the field warn of high profile papers published on human AN that were technically flawed, their interpretations going well beyond what the data could support; some have never been reproduced (these aspects are thoroughly reviewed in Oppenheim, 2018;Duque and Spector, 2019). Apart from the soundness of data, a strong species bias exists in the neurogenesis literature, due to an overestimation of the universality of laboratory rodents as animal models (Amrein, 2015;Lipp and Bonfanti, 2016;Bolker, 2017;Faykoo-Martinez et al, 2017;Oppenheim, 2019).…”

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confidence: 99%

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Brain Structural Plasticity: From Adult Neurogenesis to Immature Neurons

2020

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Brain structural plasticity is an extraordinary tool that allows the mature brain to adapt to environmental changes, to learn, to repair itself after lesions or disease, and to slow aging. A long history of neuroscience research led to fascinating discoveries of different types of plasticity, involving changes in the genetically determined structure of nervous tissue, up to the ultimate dream of neuronal replacement: a stem cell-driven "adult neurogenesis" (AN). Yet, this road does not seem a straight one, since mutable dogmas, conflicting results and conflicting interpretations continue to warm the field. As a result, after more than 10,000 papers published on AN, we still do not know its time course, rate or features with respect to other kinds of structural plasticity in our brain. The solution does not appear to be behind the next curve, as differences among mammals reveal a very complex landscape that cannot be easily understood from rodents models alone. By considering evolutionary aspects, some pitfalls in the interpretation of cell markers, and a novel population of undifferentiated cells that are not newly generated [immature neurons (INs)], we address some conflicting results and controversies in order to find the right road forward. We suggest that considering plasticity in a comparative framework might help assemble the evolutionary, anatomical and functional pieces of a very complex biological process with extraordinary translational potential.

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“…134 The low levels of neurogenesis coupled with the poor preservation of human samples have fueled controversy about the mere existence of human hippocampal neurogenesis at postnatal ages. [134][135][136][137] In an effort to resolve this controversy, we asked whether the temporal profiles of human hippocampal neurogenesis are unusual in humans compared with other species once cross-species variation in developmental schedules are accounted for. 132 Based on temporal profiles of hippocampal neurogenesis in model organisms, human hippocampal neurogenesis should drop sharply during childhood to hard to detect levels around adolescence, 132 which is consistent with that reported by.…”

Section: Appropriate Norming Procedures To Compare Brain Developmenmentioning

confidence: 99%

Closing the gap from transcription to the structural connectome enhances the study of connections in the human brain

Charvet

2020

Developmental Dynamics

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The brain is composed of a complex web of networks but we have yet to map the structural connections of the human brain in detail. Diffusion MR imaging is a high‐throughput method that relies on the principle of diffusion to reconstruct tracts (ie, pathways) across the brain. Although diffusion MR tractography is an exciting method to explore the structural connectivity of the brain in development and across species, the tractography has at times led to questionable interpretations. There are at present few if any alternative methods to trace structural pathways in the human brain. Given these limitations and the potential of diffusion MR imaging to map the human connectome, it is imperative that we develop new approaches to validate neuroimaging techniques. I discuss our recent studies integrating neuroimaging with transcriptional and anatomical variation across humans and other species over the course of development and in adulthood. Developing a novel framework to harness the potential of diffusion MR tractography provides new and exciting opportunities to study the evolution of developmental mechanisms generating variation in connections and bridge the gap between model systems to humans.

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A balanced evaluation of the evidence for adult neurogenesis in humans: implication for neuropsychiatric disorders

Cited by 42 publications

References 114 publications

Neuron-glia interaction through Serotonin-BDNF-NGFR axis enables regenerative neurogenesis in Alzheimer’s model of adult zebrafish brain

Neuron-glia interaction through Serotonin-BDNF-NGFR axis enables regenerative neurogenesis in Alzheimer’s model of adult zebrafish brain

Brain Structural Plasticity: From Adult Neurogenesis to Immature Neurons

Closing the gap from transcription to the structural connectome enhances the study of connections in the human brain

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