• Retaj Al Harbi and Abdeslam Mouihate.
• Department of Physiology, College of Medicine, Health Sciences Centre, Kuwait University, P.O. Box 24923, Safat 13110, Kuwait.
• Neuroscience. 2025 Jan 28; 568: 399407399-407.

AbstractMaternal immune activation (MIA) induces long-term cognitive impairments by modulating the gamma-aminobutyric acid (GABA)ergic system. Experimental evidence suggests that maternal immune challenge with bacterial active ingredient lipopolysaccharide (LPS) reduces GABAergic tone in the offspring's prefrontal cortex. In this study, we aimed to assess whether interleukin-6 (IL-6) contributes to this reduced GABAergic system in the prefrontal cortex of juvenile offspring. Pregnant rats were given intraperitoneal injections of either LPS (100 µg/Kg) or a pyrogen-free saline solution in the absence or the presence of an IL-6 neutralizing antibody (IL-6Ab, 10 µg/Kg) on gestation day (GD) 15, GD17 and GD19. Parvalbumin and somatostatin GABAergic interneurons and the density of inhibitory synapses were monitored in 30-day-old male and female rat offspring using fluorescent immunohistochemistry. The expression levels of Cl- transporters (NKCC1 and KCC2) were assessed using western blotting. Prenatal LPS induced a significant reduction in the cell density of parvalbumin-containing interneurons in the prefrontal cortex of female but not male rat offspring. LPS-induced MIA led to a reduction in the expression levels of NKCC1 in the prefrontal cortices of both male and female offspring. These long-lasting impacts of the MIA were alleviated when the IL-6Ab was co-administered with LPS during pregnancy. This study shows that the GABAergic system in the prefrontal cortex of female rats is highly sensitive to prenatal immune challenges. These data pave the way for exploring the specific mechanism(s) underlying the sex-dependent effects of early-life immune challenges.Copyright © 2025 International Brain Research Organization (IBRO). Published by Elsevier Inc. All rights reserved.

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