Akademik Veri Yönetim Sistemi
International Behavioral Neuroscience Society (IBNS) Annual Meeting, Tromso, Norveç, 24 Haziran 2025, (Özet Bildiri)
Autism Spectrum Disorders (ASD) are neurodevelopmental disorders characterized with disrupted communication and social interactions. This study investigates whether inhibiting visfatin, the rate-limiting enzyme of salvage pathway in NAD+ biosynthesis, during pregnancy induces ASD-like behaviors. The effects were compared to a valproic acid (VPA)-induced ASD model. Prenatal exposure to VPA increases ASD risk and alters NAD+ levels, which have been linked to ASD-related symptoms. Pregnant Wistar Albino rats received i.p. injections on embryonic day 12. Groups are as follow; A) 1 ml/kg saline; B) 1 ml/kg vehicle (1:1 DMSO); C) 400 mg/kg/ml VPA in vehicle; D) 10 mg/kg/ml visfatin inhibitor (FK866) in vehicle; E) 10 mg/kg/ml FK866+ 400 mg/kg/ml VPA in vehicle. 12 male pups per group from 40 mothers were tested for behavioral parameters to assess model validity. Pups underwent olfactory discrimination (OD) on postnatal day 9 (P9), sociability on P25, and locomotion on P30. Statistical analyses were conducted using Student’s t-test, Kruskal-Wallis and 1-Way ANOVA in Sigma-Plot. The study was approved by Bursa Uludağ University ethics committee (2022-12/08) and received funding from Bursa Uludağ University Scientific Research Projects Unit (TGA-2023-1400). Pups that were exposed to vehicle alone showed no differences compared to saline, therefore results are given between groups B, C, D and E. Latency to reach mother bedding in OD was significantly higher in groups C, D and E compared to group B (p=0.010; p<0.001; p<0.001). In sociability, groups C, D and E spent significantly less time in the chamber containing the stranger rat compared to group B (p<0.05; p<0.05; p<0.05). Groups C, D and E travelled significantly less (p<0.001; p<0.001; p<0.001) and spent significantly more time immobile (p<0.001; p<0.001; p<0.001) compared to group B in locomotion. It has been reported that the levels of NAD-consuming enzymes, such as sirtuins and CD38 in the salvage pathway, vary in ASD. The development of ASD-like behaviors was investigated through visfatin inhibition, using behavioral tests commonly employed to validate ASD models. The results suggest that inhibition of NAD+ production may trigger behavioral changes associated with ASD.