Zeid_2026_Tissue.Cell_101_103462

Lead (Pb) exposure during development remains a major neurodevelopmental hazard due to its persistence and ability to cross the placental barrier. While oxidative stress and metabolic disruption are recognized mechanisms of Pb neurotoxicity, the combined impact on neuroinflammation and epigenetic regulation is less understood. This study investigated maternal Pb exposure effects on male rat offspring, focusing on glucose metabolism, oxidative stress, neuroinflammatory markers, miR-144 expression, and histopathology. Pregnant Wistar rats were divided into two groups (n = 10/group): controls receiving deionized water and Pb-treated dams administered 5 mg/kg/day Pb powder via oral gavage from gestational day 5 to postnatal day 14. Offspring were evaluated for body and brain weight, glucose metabolism enzymes (HK, PFK-1, PK, G6PD), oxidative stress markers (MDA, CAT, GSH), neuroinflammatory mediators (IL-1beta, TGF-beta, 3-nitrotyrosine), and miR-144 expression using qRT-PCR. Additionally, cholinergic and glial activation were assessed via acetylcholinesterase (AChE) activity and glial markers GFAP and Iba-1. Pb exposure significantly reduced body and brain weight, elevated free glucose, and suppressed glycolytic enzyme activities. Oxidative stress was evident by increased MDA and depleted CAT and GSH. Neuroinflammation was confirmed by elevated IL-1beta, TGF-beta, 3-nitrotyrosine, and marked increases in AChE, GFAP, and Iba-1. miR-144 was downregulated, and histology revealed neuronal apoptosis and vascular congestion. These findings highlight interconnected mechanisms of Pb neurotoxicity involving metabolic dysfunction, oxidative damage, glial activation, and epigenetic dysregulation, identifying miR-144 as a potential biomarker and therapeutic target.