KYNA/Ahr Signaling Suppresses Neural Stem Cell Plasticity and Neurogenesis in Adult Zebrafish Model of Alzheimer's Disease.
Alzheimer Disease
/ pathology
Animals
Brain
/ metabolism
Cell Proliferation
Cohort Studies
Disease Models, Animal
Humans
Kynurenic Acid
/ metabolism
Models, Biological
Neural Stem Cells
/ metabolism
Neurogenesis
Neuronal Plasticity
Receptors, Aryl Hydrocarbon
/ metabolism
Signal Transduction
Transcriptome
/ genetics
Zebrafish
/ metabolism
Zebrafish Proteins
/ genetics
Alzheimer’s disease
kynurenic acid
neural stem cell
neurogenesis
plasticity
proliferation
regeneration
transcriptome-wide association study
zebrafish
Journal
Cells
ISSN: 2073-4409
Titre abrégé: Cells
Pays: Switzerland
ID NLM: 101600052
Informations de publication
Date de publication:
14 10 2021
14 10 2021
Historique:
received:
23
09
2021
revised:
05
10
2021
accepted:
08
10
2021
entrez:
23
10
2021
pubmed:
24
10
2021
medline:
15
12
2021
Statut:
epublish
Résumé
Neurogenesis decreases in Alzheimer's disease (AD) patients, suggesting that restoring the normal neurogenic response could be a disease modifying intervention. To study the mechanisms of pathology-induced neuro-regeneration in vertebrate brains, zebrafish is an excellent model due to its extensive neural regeneration capacity. Here, we report that Kynurenic acid (KYNA), a metabolite of the amino acid tryptophan, negatively regulates neural stem cell (NSC) plasticity in adult zebrafish brain through its receptor, aryl hydrocarbon receptor 2 (Ahr2). The production of KYNA is suppressed after amyloid-toxicity through reduction of the levels of Kynurenine amino transferase 2 (KAT2), the key enzyme producing KYNA. NSC proliferation is enhanced by an antagonist for Ahr2 and is reduced with Ahr2 agonists or KYNA. A subset of Ahr2-expressing zebrafish NSCs do not express other regulatory receptors such as
Identifiants
pubmed: 34685728
pii: cells10102748
doi: 10.3390/cells10102748
pmc: PMC8534484
pii:
doi:
Substances chimiques
Receptors, Aryl Hydrocarbon
0
Zebrafish Proteins
0
Kynurenic Acid
H030S2S85J
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Deutsche Forschungsgemeinschaft
ID : 386893015
Organisme : German Center for Neurodegenerative Diseases
ID : VH-NG-1021
Organisme : National Institute of Health
ID : R56AG069118
Organisme : National Institute of Health
ID : R56AG066889
Organisme : National Institute of Health
ID : R56AG051876
Organisme : National Institute of Health
ID : R01AG067501
Organisme : NIA NIH HHS
ID : RC2 AG036547
Pays : United States
Organisme : NIA NIH HHS
ID : U01 AG046139
Pays : United States
Organisme : NIA NIH HHS
ID : P50 AG016574
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG032990
Pays : United States
Organisme : NIA NIH HHS
ID : U01 AG046139
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG018023
Pays : United States
Organisme : NIA NIH HHS
ID : U01 AG006786
Pays : United States
Organisme : NIA NIH HHS
ID : U01 AG006786
Pays : United States
Organisme : NIA NIH HHS
ID : P01 AG017216
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG039495
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS080820
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS080820
Pays : United States
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