Scopus İndeksli Yayınlar Koleksiyonu / Scopus Indexed Publications Collection

Permanent URI for this collectionhttps://hdl.handle.net/11147/7148

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  • Article
    Notum1a Inhibition Promotes Neurogenesis in the Adult Zebrafish Brain
    (Nature Portfolio, 2025) Kocagoz, Yigit; Erdogan, Nuray Sogunmez; Ozdinc, Sevval; Ipekgil, Dogac; Katkat, Esra; Ozhan, Gunes
    Notum is a carboxylesterase enzyme that modulates extracellular signaling by hydrolyzing palmitoleoyl residues from proteins, thereby influencing key pathways involved in cell differentiation, survival, and proliferation. While notum1 expression has been identified in the brain, its role in adult neurogenesis remains poorly understood. Using the adult zebrafish brain as a model system, we demonstrate that the notum1a homolog is broadly expressed across various brain cell types but is absent in undifferentiated radial glial cells. Pharmacological inhibition of Notum activity with the small molecule inhibitor ABC99 stimulates activation of radial glial cells, leading to increased neurogenesis. A BrdU pulse-chase assay confirms that ABC99-induced proliferation enhances the production of mature neurons. Despite Notum's established role in Wnt signaling, transcriptional analysis following ABC99 treatment reveals no sustained impact on Wnt pathway targets, suggesting that Notum may regulate neurogenesis through alternative mechanisms. Our findings highlight notum1a as a potential modulator of neural progenitor cell dynamics in the adult brain and suggest that targeting Notum could represent a novel therapeutic strategy for neurodegenerative conditions characterized by impaired neurogenesis.
  • Article
    Citation - WoS: 1
    Citation - Scopus: 1
    The Role of Trna Fragments on Neurogenesis Alteration by H2o2-Induced Oxidative Stress
    (Springernature, 2025) Karacicek, Bilge; Katkat, Esra; Binokay, Leman; Ozhan, Gunes; Karakulah, Goekhan; Genc, Sermin
    Transfer RNAs (tRNAs) are small non-coding RNA molecules transcribed from tRNA genes. tRNAs cleaved into a diverse population tRNA fragments (tRFs) ranging in length from 18 to 40 nucleotides, they interact with RNA binding proteins and influence the stability and translation. Stress is one of the reasons for tRFs cleavage. In our study, we modeled oxidative stress conditions with hydrogen peroxide (H2O2) exposure and dealt with one of the frequently expressed tRF in the hippocampus region of the brain, which is tRF-Glu-CTC. For this purpose, neural stem cells (NSCs) were exposed to H2O2, and tRF-Glu-CTC levels were increased in various H(2)O(2 )concentrations. A decrease was seen in microtubule-associated protein 2 (MAP2) marker expression. To understand the H(2)O(2)oxidative stress condition on the expression of tRNA fragments, 72 hpf zebrafish embryos exposed to different H(2)O(2 )concentrations, an increase in the level of tRF-Glu-CTC was observed in all concentrations of H(2)O(2 )compared to control. Subsequently, neurogenesis markers were figured out via Calb2a (calbindin 2a) in situ hybridization (ISH) and HuC/D immunofluorescence staining (IF) staining experiments. Under H(2)O(2 )exposure, a decline was observed in Calb2a and HuC/D markers. To understand the inhibitory role of tRF-Glu-CTC on neurogenesis, NSCs were transfected via tRF-Glu-CTC inhibitor, and neurogenesis markers (ss III-tubulin, MAP2, and GFAP) were determined with qRT-PCR and IF staining. tRF-Glu-CTC inhibitor reversed the diminished neuronal markers expression under the exposure of H2O2. Gene Ontology (GO) enrichment analysis showed us that targets of tRF-Glu-CTC are generally related to neuronal function and synaptic processes.