ABSTRACT Autism spectrum disorder (ASD) arises from interactions between genetic predisposition and prenatal environmental insults. Prostaglandin E 2 (PGE 2 ), 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 PGE 2 , 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 PGE 2 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 PGE 2 signaling, leading to oxidative stress, altered autophagy‐related signaling, and glial activation, which together contribute to ASD‐relevant behavioral outcomes.
Akbaş et al. (Fri,) studied this question.