Altered glutathione homeostasis in animals prenatally exposed to lipopolysaccharide
Open accessAbstract
We previously reported that injection of bacterial lipopolysaccharide (LPS) into gravid female rats at embryonic day 10.5 resulted in a birth of offspring with fewer than normal dopamine (DA) neurons along with innate immunity dysfunction and many characteristics seen in Parkinson's disease (PD) patients. The LPS-exposed animals were also more susceptible to secondary toxin exposure as indicated by an accelerated DA neuron loss. Glutathione (GSH) is an important antioxidant in the brain. A disturbance in glutathione homeostasis has been proposed for the pathogenesis of PD. In this study, animals prenatally exposed to LPS were studied along with an acute intranigral LPS injection model for the status of glutathione homeostasis, lipid peroxidation, and related enzyme activities. Both prenatal LPS exposure and acute LPS injection produced a significant GSH reduction and increase in oxidized GSH (GSSG) and lipid peroxide (LPO) production. Activity of gamma-glutamylcysteine synthetase (GCS), the rate-limiting enzyme in de novo GSH synthesis, was up-regulated in acute supranigral LPS model but was reduced in the prenatal LPS model. The GCS light subunit protein expression was also down-regulated in prenatal LPS model. GSH redox recycling enzyme activities (glutathione peroxidase, GPx and glutathione reducdase, GR) and glutathione-S-transferase (GST), gamma-glutamyl transpeptidase (gamma-GT) activities were all increased in prenatal LPS model. Prenatal LPS exposure and aging synergized in GSH level and GSH-related enzyme activities except for those (GR, GST, and gamma-GT) with significant regional variations. Additionally, prenatal LPS exposure produced a reduction of DA neuron count in the substantia nigra (SN). These results suggest that prenatal LPS exposure may cause glutathione homeostasis disturbance in offspring brain and render DA neurons susceptible to the secondary neurotoxin insult.
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Prenatal LPS exposure reduced the level of glutathione in the brain.
“An animal study indicated that prenatal LPS exposure reduced the level of glutathione in the brain38.”
From Altered composition and function of intestinal microbiota in autism spectrum disorders: A systematic review (2019) · cites this paper as [38]
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- Authors
- ZHU, Y., CARVEY, P., & LING, Z.
- Affiliations
- Rush University Medical Center (US)
- Corresponding author
- LING, Z
- Venue
- Neurochemistry International
- Publisher
- Elsevier BV
- Published
- 2007-03
- Volume
- 50
- Issue
- 4
- Pages
- 671-680
- ISSN
- 0197-0186 (ISSN-L)
- PMC
- PMC1868495
- OpenAlex
- W2087444254
- Cited by
- 85
- References
- 30
- Citations by year
- 2025: 5 · 2024: 10 · 2023: 2 · 2022: 6 · 2021: 4 · 2020: 5 · 2019: 2 · 2018: 5 · 2017: 6 · 2016: 4 · 2015: 6 · 2013: 6 · 2012: 4
- FWCI
- 3.23
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Neurochemistry International (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Michael J. Fox Foundation for Parkinson's Research
- Bristol-Myers Squibb
- University of Washington
- National Institutes of Health (5r01ns045316-03)
- National Institute of Neurological Disorders and Stroke (NS045316, R01 NS045316-04, R01 NS045316-02, R01 NS045316-03, R01 NS045316-01, R01 NS045316)
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glutathione Transferases and Polymorphisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Keywords
- glutathione homeostasis, dopaminergic neurons, Parkinson's disease, substantia nigra, gamma-glutamylcysteine synthetase, lipid peroxidation, glutathione S-transferase, glutathione peroxidase, glutathione reductase, gamma-glutamyl transferase, neurotoxicity, innate immunity, aging, oxidative stress
- MeSH terms
- Aging, Animals, Animals, Newborn, Dopamine, Encephalitis, Enzyme Activation, Female, Glutathione, Homeostasis, Lipopolysaccharides, Male, Nerve Degeneration, Neurons, Parkinson Disease, Pregnancy, Prenatal Exposure Delayed Effects, Substantia Nigra, Lipid Peroxidation, Causality, Cell Death, Rats, Sprague-Dawley, Oxidative Stress, Inflammation Mediators, Rats
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