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

by Prabesh Bhattarai, Mehmet Ilyas Cosacak, Violeta Mashkaryan, Sevgican Demir, Stanislava Dimitrova Popova, Nambirajan Govindarajan, Kerstin Brandt, Yixin Zhang, Weipang Chang, Konstantinos Ampatzis, Caghan Kizil 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 th at 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 neuron s. 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 regenerat ive neurogenesis after AD conditions in zebrafish.
Source: PLoS Biology: Archived Table of Contents - Category: Biology Authors: Source Type: research