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

It was recently suggested that supplying the brain with new neurons could counteract Alzheimer's disease (AD). This provocative idea requires further testing in experimental models in which the molecular basis of disease-induced neuronal regeneration could be investigated. We previously found t...

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Main Authors: Prabesh Bhattarai, Mehmet Ilyas Cosacak, Violeta Mashkaryan, Sevgican Demir, Stanislava Dimitrova Popova, Nambirajan Govindarajan, Kerstin Brandt, Yixin Zhang, Weipang Chang, Konstantinos Ampatzis, Caghan Kizil
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2020-01-01
Series:PLoS Biology
Online Access:https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.3000585&type=printable
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author Prabesh Bhattarai
Mehmet Ilyas Cosacak
Violeta Mashkaryan
Sevgican Demir
Stanislava Dimitrova Popova
Nambirajan Govindarajan
Kerstin Brandt
Yixin Zhang
Weipang Chang
Konstantinos Ampatzis
Caghan Kizil
author_facet Prabesh Bhattarai
Mehmet Ilyas Cosacak
Violeta Mashkaryan
Sevgican Demir
Stanislava Dimitrova Popova
Nambirajan Govindarajan
Kerstin Brandt
Yixin Zhang
Weipang Chang
Konstantinos Ampatzis
Caghan Kizil
author_sort Prabesh Bhattarai
collection DOAJ
description It was recently suggested that supplying the brain with new neurons could counteract Alzheimer's disease (AD). This provocative idea requires further testing in experimental models in which 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 AD and could help to understand the mechanisms to be harnessed for developing new neurons in diseased mammalian brains. Here, by performing single-cell transcriptomics, we found that amyloid toxicity-induced interleukin-4 (IL4) promotes NSC proliferation and neurogenesis by suppressing the tryptophan metabolism and reducing the production of serotonin. NSC proliferation was suppressed by serotonin via down-regulation of brain-derived neurotrophic factor (BDNF)-expression in serotonin-responsive periventricular neurons. BDNF enhances NSC plasticity and neurogenesis via nerve growth factor receptor A (NGFRA)/ nuclear factor 'kappa-light-chain-enhancer' of activated B-cells (NFkB) signaling in zebrafish but not in rodents. Collectively, our results suggest a complex neuron-glia interaction that regulates regenerative neurogenesis after AD conditions in zebrafish.
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issn 1544-9173
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language English
publishDate 2020-01-01
publisher Public Library of Science (PLoS)
record_format Article
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spelling doaj-art-8d5216d5f4864241a8d4ccbdf3cf52d22025-08-20T02:55:20ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852020-01-01181e300058510.1371/journal.pbio.3000585Neuron-glia interaction through Serotonin-BDNF-NGFR axis enables regenerative neurogenesis in Alzheimer's model of adult zebrafish brain.Prabesh BhattaraiMehmet Ilyas CosacakVioleta MashkaryanSevgican DemirStanislava Dimitrova PopovaNambirajan GovindarajanKerstin BrandtYixin ZhangWeipang ChangKonstantinos AmpatzisCaghan KizilIt was recently suggested that supplying the brain with new neurons could counteract Alzheimer's disease (AD). This provocative idea requires further testing in experimental models in which 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 AD and could help to understand the mechanisms to be harnessed for developing new neurons in diseased mammalian brains. Here, by performing single-cell transcriptomics, we found that amyloid toxicity-induced interleukin-4 (IL4) promotes NSC proliferation and neurogenesis by suppressing the tryptophan metabolism and reducing the production of serotonin. NSC proliferation was suppressed by serotonin via down-regulation of brain-derived neurotrophic factor (BDNF)-expression in serotonin-responsive periventricular neurons. BDNF enhances NSC plasticity and neurogenesis via nerve growth factor receptor A (NGFRA)/ nuclear factor 'kappa-light-chain-enhancer' of activated B-cells (NFkB) signaling in zebrafish but not in rodents. Collectively, our results suggest a complex neuron-glia interaction that regulates regenerative neurogenesis after AD conditions in zebrafish.https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.3000585&type=printable
spellingShingle Prabesh Bhattarai
Mehmet Ilyas Cosacak
Violeta Mashkaryan
Sevgican Demir
Stanislava Dimitrova Popova
Nambirajan Govindarajan
Kerstin Brandt
Yixin Zhang
Weipang Chang
Konstantinos Ampatzis
Caghan Kizil
Neuron-glia interaction through Serotonin-BDNF-NGFR axis enables regenerative neurogenesis in Alzheimer's model of adult zebrafish brain.
PLoS Biology
title Neuron-glia interaction through Serotonin-BDNF-NGFR axis enables regenerative neurogenesis in Alzheimer's model of adult zebrafish brain.
title_full Neuron-glia interaction through Serotonin-BDNF-NGFR axis enables regenerative neurogenesis in Alzheimer's model of adult zebrafish brain.
title_fullStr Neuron-glia interaction through Serotonin-BDNF-NGFR axis enables regenerative neurogenesis in Alzheimer's model of adult zebrafish brain.
title_full_unstemmed Neuron-glia interaction through Serotonin-BDNF-NGFR axis enables regenerative neurogenesis in Alzheimer's model of adult zebrafish brain.
title_short Neuron-glia interaction through Serotonin-BDNF-NGFR axis enables regenerative neurogenesis in Alzheimer's model of adult zebrafish brain.
title_sort neuron glia interaction through serotonin bdnf ngfr axis enables regenerative neurogenesis in alzheimer s model of adult zebrafish brain
url https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.3000585&type=printable
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