Late N‐acetylcysteine treatment prevents the deficits induced in the offspring of dams exposed to an immune stress during gestation
Abstract
Prenatal infection is a major stressful experience leading to enhanced susceptibility for mental illnesses in humans. We recently reported in rats, that oxidative stress and glutathione (GSH) shortage occurred in fetal male brain after lipopolysaccharide (LPS) to the dams and that these responses might be involved in the neurodevelopmental deficits observed in adolescent offspring. Furthermore, pretreatment with N‐acetylcysteine (NAC) before LPS avoided both delayed synaptic plasticity and mnesic performance deficits. Since NAC is one of the few medications permitted in pregnant women, this study evaluated the ability of NAC to serve as a protective therapy even after the LPS challenge. Pregnant rats received a single ip injection of E. coli LPS, two days before delivery, and were given NAC in their tap water after the LPS. GSH was evaluated at the time of its expected drop in the hippocampus of male fetuses, whereas long‐term potentiation (LTP) in the CA1 area of the hippocampus and spatial memory in the water‐maze were recorded in 28‐day‐old male offspring. Post‐treatment with NAC, four hours after the LPS challenge fully prevented the drop in the GSH hippocampal content. LTP, as well as spatial learning were completely protected. NAC administration at delivery also partially restored the LTP whereas post‐treatment two days later was inefficient. Another set of dams were supplemented with α‐tocopherol prior to LPS exposure, enhancing the α‐tocopherol levels in fetal hippocampus. This treatment did not prevent the LPS‐induced synaptic plasticity impairment. These results point to fetal hippocampal GSH as a major target of the detrimental effects of in utero LPS challenge. The therapeutic window of NAC extends up to birth, suggesting that this drug might be clinically useful even after an immuno‐inflammatory episode. © 2008 Wiley‐Liss, Inc.
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Disruption of NFE2L2 induces NF-κB activation, probably by modifying NFKB1A degradation and NF-κB binding to DNA.
“At the molecular level, the antagonism between antioxidant-promoting NFE2L2 and inflammatory gene-regulating NF-κB may control the balance between oxidative stress and inflammation 94 : disruption of NFE2L2 induces NF-κB activation, probably by modifying NF-κB inhibitor α (NFKB1A, also known as IkBα) degradation and NF-κB binding to DNA 95,96”
From Linking early-life NMDAR hypofunction and oxidative stress in schizophrenia pathogenesis (2016) · cites this paper as [95]
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- Authors
- Lanté, F., Meunier, J., Guiramand, J., De Jesus Ferreira, M., Cambonie, G., Aimar, R., Cohen‐Solal, C., Maurice, T., Vignes, M., & Barbanel, G.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Inserm (FR)
- Corresponding author
- Barbanel, Gérard
- ORCID
- Venue
- Hippocampus
- Publisher
- Wiley
- Published
- 2008-02-27
- Volume
- 18
- Issue
- 6
- Pages
- 602-609
- ISSN
- 1050-9631 (ISSN-L)
- 1098-1063
- OpenAlex
- W2056901364
- Cited by
- 124
- References
- 49
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 4 · 2023: 2 · 2022: 1 · 2021: 6 · 2020: 9 · 2019: 6 · 2018: 6 · 2017: 14 · 2016: 10 · 2015: 9 · 2014: 11 · 2013: 6 · 2012: 13
- FWCI
- 7.91
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Hippocampus (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Funders
- Fondation pour la Recherche Médicale
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Maternal Mental Health During Pregnancy and Postpartum
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Neuroscience › Developmental Neuroscience › Anesthesia and Neurotoxicity Research
- Keywords
- N-acetylcysteine, lipopolysaccharide, maternal infection, glutathione depletion, oxidative stress, fetal hippocampus, long-term potentiation, synaptic plasticity, spatial memory, alpha-tocopherol, neurodevelopmental deficits, therapeutic window
- MeSH terms
- Acetylcysteine, Animals, Antioxidants, Drug Administration Schedule, Drug Evaluation, Preclinical, Female, Glutathione, Hippocampus, Lipopolysaccharides, Male, Memory Disorders, Pregnancy, Pregnancy Complications, Prenatal Exposure Delayed Effects, Rats, Sprague-Dawley, Long-Term Potentiation, Neuroprotective Agents, Maze Learning, Maternal Exposure, Endotoxemia, alpha-Tocopherol, Rats
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