Open AccessNeuron-glia interaction through Serotonin-BDNF-NGFR axis enables regenerative neurogenesis in Alzheimer’s model of adult zebrafish brain
Author(s) -
Prabesh Bhattarai,
Mehmet İlyas Coşacak,
Violeta Mashkaryan,
Sevgican Demir,
Stanislava Popova,
Nambirajan Govindarajan,
Kerstin Brandt,
Yixin Zhang,
WeiKuo Chang,
Konstantinos Ampatzis,
Çağhan Kızıl
Publication year - 2020
Publication title -
plos biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.127
H-Index - 271
eISSN - 1545-7885
pISSN - 1544-9173
DOI - 10.1371/journal.pbio.3000585
Subject(s) - neurogenesis , zebrafish , biology , neuroscience , neurotrophic factors , brain derived neurotrophic factor , neural stem cell , neurotrophin , neuron , microbiology and biotechnology , stem cell , receptor , biochemistry , gene
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.