PUBLICATION

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

Authors
Bhattarai, P., Cosacak, M.I., Mashkaryan, V., Demir, S., Popova, S.D., Govindarajan, N., Brandt, K., Zhang, Y., Chang, W., Ampatzis, K., Kizil, C.
ID
ZDB-PUB-200108-10
Date
2020
Source
PLoS Biology   18: e3000585 (Journal)
Registered Authors
Bhattarai, Prabesh, Brandt, Kerstin, Cosacak, Mehmet Ilyas, Kizil, Caghan
Keywords
none
Datasets
GEO:GSE124162, GEO:GSE118599
MeSH Terms
  • Neuroglia/physiology*
  • Receptors, Nerve Growth Factor/genetics
  • Receptors, Nerve Growth Factor/metabolism
  • Cell Communication/physiology*
  • Male
  • Serotonin/genetics
  • Serotonin/metabolism
  • Neuroimmunomodulation/physiology
  • Age Factors
  • Animals
  • Disease Models, Animal
  • Nerve Regeneration/genetics
  • Nerve Regeneration/physiology*
  • Neuronal Plasticity/physiology
  • Zebrafish
  • Neurogenesis/physiology*
  • Neural Stem Cells/pathology
  • Neural Stem Cells/physiology
  • Animals, Genetically Modified
  • Signal Transduction/genetics
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
  • Brain/metabolism
  • Brain/physiology
  • Neurons/physiology*
  • Alzheimer Disease*/genetics
  • Alzheimer Disease*/pathology
  • Alzheimer Disease*/physiopathology
  • Mice
  • Mice, Transgenic
  • Brain-Derived Neurotrophic Factor/genetics
  • Brain-Derived Neurotrophic Factor/metabolism
(all 32)
PubMed
31905199 Full text @ PLoS Biol.
Abstract
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.
Genes / Markers
Figures
Figure Gallery (6 images)
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Expression
Phenotype
No data available
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
nc1TgTransgenic Insertion
    y83TgTransgenic Insertion
      1 - 2 of 2
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      Human Disease / Model
      Human Disease Fish Conditions Evidence
      Alzheimer's diseaseTAS
      1 - 1 of 1
      Show
      Sequence Targeting Reagents
      Target Reagent Reagent Type
      ngfraMO1-ngfraMRPHLNO
      1 - 1 of 1
      Show
      Fish
      Fish
      AB
      1 - 1 of 1
      Show
      Antibodies
      Orthology
      No data available
      Engineered Foreign Genes
      Marker Marker Type Name
      EGFPEFGEGFP
      1 - 1 of 1
      Show
      Mapping
      No data available
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      Citation
      Bhattarai, P., Cosacak, M.I., Mashkaryan, V., Demir, S., Popova, S.D., Govindarajan, N., Brandt, K., Zhang, Y., Chang, W., Ampatzis, K., Kizil, C. (2020) Neuron-glia interaction through Serotonin-BDNF-NGFR axis enables regenerative neurogenesis in Alzheimer's model of adult zebrafish brain. PLoS Biology. 18:e3000585.