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

CANSIZ D., Ünal İ., Gani Sürmen M., Sürmen S., SEZER Z., Beler M., ...More

Brain Research, vol.1836, 2024 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 1836
  • Publication Date: 2024
  • Doi Number: 10.1016/j.brainres.2024.148952
  • Journal Name: Brain Research
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, PASCAL, Animal Behavior Abstracts, Aquatic Science & Fisheries Abstracts (ASFA), BIOSIS, CAB Abstracts, Chemical Abstracts Core, EMBASE, Linguistics & Language Behavior Abstracts, Psycinfo, Veterinary Science Database
  • Keywords: Gentisic acid, Gut-brain axis, LC-MS/MS analyzes, Parkinson's disease, Rotenone, Zebrafish
  • Istanbul Medipol University Affiliated: Yes


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.