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
  • Age Factors
  • Alzheimer Disease*/genetics
  • Alzheimer Disease*/pathology
  • Alzheimer Disease*/physiopathology
  • Animals
  • Animals, Genetically Modified
  • Brain/metabolism
  • Brain/physiology
  • Brain-Derived Neurotrophic Factor/genetics
  • Brain-Derived Neurotrophic Factor/metabolism
  • Cell Communication/physiology*
  • Disease Models, Animal
  • Male
  • Mice
  • Mice, Transgenic
  • Nerve Regeneration/genetics
  • Nerve Regeneration/physiology*
  • Neural Stem Cells/pathology
  • Neural Stem Cells/physiology
  • Neurogenesis/physiology*
  • Neuroglia/physiology*
  • Neuroimmunomodulation/physiology
  • Neuronal Plasticity/physiology
  • Neurons/physiology*
  • Receptors, Nerve Growth Factor/genetics
  • Receptors, Nerve Growth Factor/metabolism
  • Serotonin/genetics
  • Serotonin/metabolism
  • Signal Transduction/genetics
  • Zebrafish
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
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
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Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes