Prenatal Indomethacin Exposure Is Associated With Autism-Relevant Behavioral Alterations Linked to Oxidative Stress and Altered Autophagy-Related Signaling
Developmental Neurobiology, cilt.86, sa.3, 2026 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 86 Sayı: 3
- Basım Tarihi: 2026
- Doi Numarası: 10.1002/dneu.70041
- Dergi Adı: Developmental Neurobiology
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, EMBASE, MEDLINE, Psycinfo, Zoological Record, Natural Science Collection (ProQuest), Biological Science Database (ProQuest), Biomedical Reference Collection: Corporate Edition (EBSCO), Health Research Premium Collection (ProQuest)
- Anahtar Kelimeler: autism, neuroinflammation, prenatal neurotoxicity, prostaglandin signaling, rats
- Karadeniz Teknik Üniversitesi Adresli: Evet
Özet
Autism spectrum disorder (ASD) arises from interactions between genetic predisposition and prenatal environmental insults. Prostaglandin E2 (PGE2), derived from cyclooxygenase-2 (COX-2), regulates neuronal differentiation and glia–neuron signaling; thus, its inhibition during gestation may impair neurodevelopment. To examine whether prenatal exposure to indomethacin, a non-selective COX inhibitor, induces autism-like alterations in rats with possible sex differences. Sixteen pregnant Wistar rats received indomethacin (1 mg/kg, gavage) on Gestational Days 10–14. Adult offspring (P50–P54) underwent behavioral tests (open-field, rearing, rotarod, and three-chamber sociability). Hippocampal and cerebellar tissues were analyzed for PGE2, LC3B (ELISA), MDA (TBARS), neuronal density, and GFAP expression (CA1, CA3 – Nissl, GFAP staining). Indomethacin reduced sociability, exploration, and motor performance, especially in males, and decreased PGE2 and LC3B while increasing MDA (p < 0.001). Histologically, CA1 neuronal counts increased while GFAP immunoreactivity was markedly elevated in hippocampal (CA1 and CA3) and cerebellar regions (p < 0.05), reflecting astroglial activation and neuroinflammatory remodeling. Prenatal inhibition of prostaglandin synthesis may disturb PGE2 signaling, leading to oxidative stress, altered autophagy-related signaling, and glial activation, which together contribute to ASD-relevant behavioral outcomes.