TY  - JOUR
AU  - Bhattarai, Prabesh
AU  - Cosacak, Mehmet Ilyas
AU  - Mashkaryan, Violeta
AU  - Demir, Sevgican
AU  - Popova, Stanislava Dimitrova
AU  - Govindarajan, Nambirajan
AU  - Brandt, Kerstin
AU  - Zhang, Yixin
AU  - Chang, Weipang
AU  - Ampatzis, Konstantinos
AU  - Kizil, Caghan
TI  - Neuron-glia interaction through Serotonin-BDNF-NGFR axis enables regenerative neurogenesis in Alzheimer's model of adult zebrafish brain.
JO  - PLoS biology
VL  - 18
IS  - 1
SN  - 1545-7885
CY  - Lawrence, KS
PB  - PLoS
M1  - DZNE-2020-00492
SP  - e3000585
PY  - 2020
AB  - 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.
KW  - Age Factors
KW  - Alzheimer Disease: genetics
KW  - Alzheimer Disease: pathology
KW  - Alzheimer Disease: physiopathology
KW  - Animals
KW  - Animals, Genetically Modified
KW  - Brain: metabolism
KW  - Brain: physiology
KW  - Brain-Derived Neurotrophic Factor: genetics
KW  - Brain-Derived Neurotrophic Factor: metabolism
KW  - Cell Communication: physiology
KW  - Disease Models, Animal
KW  - Male
KW  - Mice
KW  - Mice, Transgenic
KW  - Nerve Regeneration: genetics
KW  - Nerve Regeneration: physiology
KW  - Neural Stem Cells: pathology
KW  - Neural Stem Cells: physiology
KW  - Neurogenesis: physiology
KW  - Neuroglia: physiology
KW  - Neuroimmunomodulation: physiology
KW  - Neuronal Plasticity: physiology
KW  - Neurons: physiology
KW  - Receptors, Nerve Growth Factor: genetics
KW  - Receptors, Nerve Growth Factor: metabolism
KW  - Serotonin: genetics
KW  - Serotonin: metabolism
KW  - Signal Transduction: genetics
KW  - Zebrafish
KW  - Zebrafish Proteins: genetics
KW  - Zebrafish Proteins: metabolism
KW  - Brain-Derived Neurotrophic Factor (NLM Chemicals)
KW  - Receptors, Nerve Growth Factor (NLM Chemicals)
KW  - Zebrafish Proteins (NLM Chemicals)
KW  - Serotonin (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:31905199
C2  - pmc:PMC6964913
DO  - DOI:10.1371/journal.pbio.3000585
UR  - https://pub.dzne.de/record/145133
ER  -