PubMed İndeksli Yayınlar Koleksiyonu / PubMed Indexed Publications Collection
Permanent URI for this collectionhttps://hdl.handle.net/11147/7645
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Article Epigallocatechin Gallate and Punicalagin Combination Reduces Aβ Aggregation and Promotes Neurogenesis in Adult Zebrafish Brain(John Wiley and Sons Inc, 2026) Nazli, D.; Ipekgil, D.; Poyraz, Y.K.; Can, K.; Okmen, I.; Turhanlar-Sahin, E.; Ozhan, G.Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, memory impairment, and behavioral alterations. The pathogenesis of AD involves the accumulation of amyloid-beta (Aβ) plaques and the hyperphosphorylated tau proteins, which disrupt neuronal function and trigger neuroinflammation. This study explores the therapeutic potential of epigallocatechin gallate (EGCG) and punicalagin (PU) in mitigating Aβ-induced toxicity using an adult zebrafish model of AD. Our results demonstrate that the EGCG + PU combination significantly reduces Aβ accumulation, protects against cellular damage, suppresses acetylcholinesterase (AChE) activity, and normalizes the expression of amyloidogenic and AD-related genes. Additionally, EGCG + PU treatment alleviates neuroinflammation by suppressing glial activation, including reductions in L-plastin and proinflammatory cytokine expression, while promoting neuronal recovery through mechanisms of neurogenesis and neuroprotection. Notably, the combination treatment restored neuronal density and improved behavioral outcomes by alleviating anxiety- and aggression-like behaviors associated with Aβ toxicity. These results underscore the synergistic neuroprotective effects of EGCG + PU, highlighting their potential as a novel therapeutic approach for mitigating the pathological, behavioral, and inflammatory aspects of AD. © 2026 Wiley Periodicals LLC.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, GunesNotum 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: 2Citation - Scopus: 2Tuning Toxicity Profiles of Graphene Oxide Through Imidazole-Oxime Modification: Zebrafish as a Model System(Oxford Univ Press, 2025) Yildirim, Serkan; Kokturk, Mine; Yigit, Aybek; Sahin, Ayse; Kiliclioglu, Metin; Atamanalp, Muhammed; Alak, GoncaThe increasing use of nanotechnology, especially in agriculture and the food industry, has raised concerns about the possible adverse effects of nanomaterials (NMs) on human health and the environment. This study investigates the effects of synthesized graphene oxide (GO) and its derivatives on zebrafish exposed for 96 hr, focusing on morphological changes in brain tissue, histopathology, and immunofluorescent markers such as 8-hydroxy-2'-deoxyguanosine (8-OHdG) and nucleolar protein 10 (NOP10). Exposure to GO resulted in malformations, DNA damage, and increased NOP10 expression, and it reduced hatching and survival rates. Our results demonstrated that exposure to GO, graphene oxide-oxime (GO-OX), and OX exerted dose-dependent inhibitory effects on hatching and promoted malformations in zebrafish larvae. Histopathological analysis revealed that higher doses led to more pronounced tissue damage, with GO 50 causing severe degeneration and necrosis, while high doses of GO-OX and OX resulted in moderate tissue changes. This was further supported by the increased expression levels of 8-OHdG (marker of oxidative DNA damage) and NOP10 (marker of nucleolar stress), which aligns with the histopathological findings and confirms the neurotoxic effects. Notably, GO-OX treatments consistently mitigated both morphological and neurotoxic effects at all doses, suggesting that oxime functionalization reduces the inherent toxicity of GO. In contrast, treatment with different concentrations of GO-OX derivatives mitigated these adverse effects, reducing them to mild or moderate levels.Review Citation - Scopus: 2Wnt/β-catenin Signaling in Central Nervous System Regeneration(2025) Nazli, D.; Bora, U.; Ozhan, G.The Wnt/β-catenin signaling pathway plays a pivotal role in the development, maintenance, and repair of the central nervous system (CNS). This chapter explores the diverse functions of Wnt/β-catenin signaling, from its critical involvement in embryonic CNS development to its reparative and plasticity-inducing roles in response to CNS injury. We discuss how Wnt/β-catenin signaling influences various CNS cell types-astrocytes, microglia, neurons, and oligodendrocytes-each contributing to repair and plasticity after injury. The chapter also addresses the pathway's involvement in CNS disorders such as Alzheimer's and Parkinson's diseases, psychiatric disorders, and traumatic brain injury (TBI), highlighting potential Wnt-based therapeutic approaches. Lastly, zebrafish are presented as a promising model organism for studying CNS regeneration and neurodegenerative diseases, offering insights into future research and therapeutic development. © 2024. The Author(s), under exclusive license to Springer Nature Switzerland AG.Article Citation - WoS: 1Citation - Scopus: 2<i>tubg1</I> Somatic Mutants Show Tubulinopathy-Associated Neurodevelopmental Phenotypes in a Zebrafish Model(Springer, 2024) Cark, Ozge; Katkat, Esra; Aydogdu, Ipek; Iscan, Evin; Oktay, Yavuz; Ozhan, GunesDevelopment of the multilayered cerebral cortex relies on precise orchestration of neurogenesis, neuronal migration, and differentiation, processes tightly regulated by microtubule dynamics. Mutations in tubulin superfamily genes have been associated with tubulinopathies, encompassing a spectrum of cortical malformations including microcephaly and lissencephaly. Here, we focus on gamma-tubulin, a pivotal regulator of microtubule nucleation encoded by TUBG1. We investigate its role in brain development using a zebrafish model with somatic tubg1 mutation, recapitulating features of TUBG1-associated tubulinopathies in patients and mouse disease models. We demonstrate that gamma-tubulin deficiency disrupts neurogenesis and brain development, mirroring microcephaly phenotypes. Furthermore, we uncover a novel potential regulatory link between gamma-tubulin and canonical Wnt/beta-catenin signaling, with gamma-tubulin deficiency impairing Wnt activity. Our findings provide insights into the pathogenesis of cortical defects and suggest that gamma-tubulin could be a potential target for further research in neurodevelopmental disorders, although challenges such as mode of action, specificity, and potential side effects must be addressed.