Sex-specific long-term effects of neonatal LPS exposure in rats: relevance for immune-mediated neurodevelopmental disorders
4 affiliations
- 1Department of Pharmacy, School of Medicine, University of Naples Federico II, Via Domenico Montesano, 49 - 80131 Naples, Italy
- 2Department of Clinical and Experimental Medicine, University of Foggia, Via Napoli, 20 – 71122 Foggia, Italy
- 3Department of Veterinary Medicine and Animal Production, University of Naples Federico II, Via Delpino 1, 80137 Naples, Italy
- 4Department of Drug Sciences, University of Pavia, Viale Torquato Taramelli, 12 – 27100 Pavia, Italy
Abstract
Early-life immune activation is increasingly recognized as a critical risk factor for the development of neurodevelopmental and neuropsychiatric disorders. Neonatal infections and associated inflammatory responses may impair brain development and contribute to long-term behavioral alterations in a sex-dependent manner. This study aims to investigate the effects of lipopolysaccharide (LPS) injection (1 mg/kg, i.p) on post-natal day (PND) 3 in both male and female young adult Wistar rats (PND 45). LPS challenge induced hyperactivity and anxiety-like behavior, with females displaying pronounced stereotyped movements, such as self-grooming and marble burying. Behavioral abnormalities were accompanied by region-specific alterations in GABAergic, dopaminergic, and serotonergic signaling within the cortico-striatal-thalamic circuit. LPS-induced immune activation triggered a long-lasting systemic inflammatory response and increased the expression of selected innate immune markers in the CNS. Additionally, oxidative stress was evidenced by increased striatal reactive oxygen species (ROS) production in females and enhanced lipid peroxidation characterized by overall higher 4-HNE levels observed in the striatum and thalamus of male rats. Our results suggest that early-life LPS exposure produces long-lasting behavioral and neurobiological alterations, with females showing greater susceptibility to selected behavioral and neurochemical outcomes. These findings support the utility of LPS-based models to explore how neonatal immune activation may predispose to neurodevelopmental vulnerability, offering translational insights into how early-life innate immune activation may contribute to neurodevelopmental vulnerability and psychiatric risk.
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BibTeX
@article{opallo2026sexspecific,
title = {{Sex-specific long-term effects of neonatal LPS exposure in rats: relevance for immune-mediated neurodevelopmental disorders}},
author = {Nicola Opallo and Stefania Melini and Maria Bove and Filomena Del Piano and Federica Comella and Maria Grazia Morgese and Stefania Schiavone and Maria Carmela Ferrante and Giuseppina Mattace Raso and Claudio Pirozzi and Adriano Lama and Luigia Trabace and Rosaria Meli},
journal = {Translational Psychiatry},
year = {2026},
month = aug,
doi = {10.1038/s41398-026-04359-x},
url = {https://doi.org/10.1038/s41398-026-04359-x},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Sex-specific long-term effects of neonatal LPS exposure in rats: relevance for immune-mediated neurodevelopmental disorders
AU - Nicola Opallo
AU - Stefania Melini
AU - Maria Bove
AU - Filomena Del Piano
AU - Federica Comella
AU - Maria Grazia Morgese
AU - Stefania Schiavone
AU - Maria Carmela Ferrante
AU - Giuseppina Mattace Raso
AU - Claudio Pirozzi
AU - Adriano Lama
AU - Luigia Trabace
AU - Rosaria Meli
PY - 2026
DA - 2026/08/10
JO - Translational Psychiatry
DO - 10.1038/s41398-026-04359-x
UR - https://doi.org/10.1038/s41398-026-04359-x
AB - Early-life immune activation is increasingly recognized as a critical risk factor for the development of neurodevelopmental and neuropsychiatric disorders. Neonatal infections and associated inflammatory responses may impair brain development and contribute to long-term behavioral alterations in a sex-dependent manner. This study aims to investigate the effects of lipopolysaccharide (LPS) injection (1 mg/kg, i.p) on post-natal day (PND) 3 in both male and female young adult Wistar rats (PND 45). LPS challenge induced hyperactivity and anxiety-like behavior, with females displaying pronounced stereotyped movements, such as self-grooming and marble burying. Behavioral abnormalities were accompanied by region-specific alterations in GABAergic, dopaminergic, and serotonergic signaling within the cortico-striatal-thalamic circuit. LPS-induced immune activation triggered a long-lasting systemic inflammatory response and increased the expression of selected innate immune markers in the CNS. Additionally, oxidative stress was evidenced by increased striatal reactive oxygen species (ROS) production in females and enhanced lipid peroxidation characterized by overall higher 4-HNE levels observed in the striatum and thalamus of male rats. Our results suggest that early-life LPS exposure produces long-lasting behavioral and neurobiological alterations, with females showing greater susceptibility to selected behavioral and neurochemical outcomes. These findings support the utility of LPS-based models to explore how neonatal immune activation may predispose to neurodevelopmental vulnerability, offering translational insights into how early-life innate immune activation may contribute to neurodevelopmental vulnerability and psychiatric risk.
SN - 2158-3188
ER -