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Gentisic acid exerts neuroprotective effects in neurotoxin-induced Parkinson's disease model in zebrafish: Cross-talk between pathways related with neurodegeneration in the gut-brain axis

Cansız, Derya ; Ünal, İsmail ; Gani Sürmen, Mustafa ; Sürmen, Saime ; Sezer, Zehra ; Beler, Merih ; Güzel, Elif ; Alturfan, A.Ata ; Emekli-Alturfan, Ebru

Brain research, 2024-08, Vol.1836, p.148952-148952, Article 148952 [Periódico revisado por pares]

Netherlands: Elsevier B.V

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  • Título:
    Gentisic acid exerts neuroprotective effects in neurotoxin-induced Parkinson's disease model in zebrafish: Cross-talk between pathways related with neurodegeneration in the gut-brain axis
  • Autor: Cansız, Derya ; Ünal, İsmail ; Gani Sürmen, Mustafa ; Sürmen, Saime ; Sezer, Zehra ; Beler, Merih ; Güzel, Elif ; Alturfan, A.Ata ; Emekli-Alturfan, Ebru
  • Assuntos: Animals ; Brain - drug effects ; Brain - metabolism ; Brain-Gut Axis - drug effects ; Brain-Gut Axis - physiology ; Disease Models, Animal ; Gentisic acid ; Gut-brain axis ; LC-MS/MS analyzes ; Locomotion - drug effects ; Neuroprotective Agents - pharmacology ; Neurotoxins - toxicity ; Oxidative Stress - drug effects ; Parkinson Disease - drug therapy ; Parkinson Disease - metabolism ; Parkinson's disease ; Rotenone ; Rotenone - toxicity ; Zebrafish
  • É parte de: Brain research, 2024-08, Vol.1836, p.148952-148952, Article 148952
  • Notas: ObjectType-Article-1
    SourceType-Scholarly Journals-1
    ObjectType-Feature-2
    content type line 23
  • Descrição: [Display omitted] •Rotenone changed brain and intestinal protein expressions related to oxidative phosphorylation.•Gentisic acid reversed protein expressions altered by rotenone in brain and intestines.•Gentisic acid ameliorated tyrosine hydroxylase expressing dopaminergic neurons.•Gentisic acid improved locomotor behaviors in rotenone exposed zebrafish.•Gentisic acid ameliorated oxidant-antioxidant status in brain and intestines. Given that global prevalence of Parkinson's disease (PD) is expected to rise over the next few decades, understanding the mechanisms and causes of PD is critical. With emphasis on gut-brain axis, we sought to assess the impact of gentisic acid (GA), a diphenolic compound generated from benzoic acid, in rotenone (Rot) induced PD model in zebrafish. For thirty days, adult zebrafish were exposed to GA and rotenone. Tox-Track program was used to analyze locomotor behaviors in the control, GA, Rot, and Rot + GA groups. LC-MS/MS was performed in brain and intestinal tissues. Proteome Discoverer 2.4 was used to analyze raw files, peptide lists were searched against Danio rerio proteins. Protein interactions or annotations were obtained from STRING database. Tyrosine hydroxylase (Th) staining was performed immunohistochemically in the brain. PD-related gene expressions were determined by RT-PCR. Lipid peroxidation, nitric oxide, superoxide dismutase, glutathione S-transferase, and acetylcholinesterase were measured spectrophotometrically. Improved locomotor behaviors were observed by GA treatment in Rot group as evidenced by increased average speed, exploration rate, and total distance. 5214 proteins were identified in intestinal tissues, 4114 proteins were identified in brain by LC-MS/MS. Rotenone exposure altered protein expressions related to oxidative phosphorylation in brain and intestines. Protein expressions involved in ferroptis and actin cytoskeleton changed in brain and intestines. Altered protein expressions were improved by GA. GA ameliorated Th-immunoreactivity in brain, improved park2, park7, pink1, and lrrk2 expressions. Our results show that GA may be a candidate agent to be evaluated for its potential protective effect for PD.
  • Editor: Netherlands: Elsevier B.V
  • Idioma: Inglês
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  • Realização: ABCD-USP USP   Logos de Redes Sociais: Freepik

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