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Quantitative profiling of neurotransmitter abnormalities in the hippocampus of rats treated with lipopolysaccharide: Focusing on kynurenine pathway and implications for depression
- Source :
- Journal of Neuroimmunology. :41-46
- Publication Year :
- 2016
- Publisher :
- Elsevier BV, 2016.
-
Abstract
- Peripheral administration of lipopolysaccharide (LPS) can induce the rodents to a depression-like state accompanied with remarkable changes of neurotransmitter systems. In this study, the effect of an intraperitoneal LPS injection (3 mg/kg) on the concentrations of neurotransmitters was investigated by in vivo microdialysis in rat hippocampus. To further explore dysregulation pattern of the neurotransmitters following continuous inflammatory process, we then analyzed the neurotransmitters in the hippocampus of rats after 2-week LPS exposure (500 μg/kg every other day). Acute treatment of LPS quickly enhanced glutamate release and increased the extracellular levels of dopamine, serotonin and their metabolites. Elevated glutamate status was also found in the chronic inflamed hippocampus, whereas dopamine and serotonin was decreased following prolonged LPS exposure. Interestingly, both acute and chronic treatment of LPS significantly elevated hippocampal kynurenine concentrations and altered the balance between the serotonin and kynurenine branches of tryptophan metabolism—increasing kynurenine/tryptophan ratio, but decreasing serotonin/tryptophan ratio. Additionally, kynurenic acid, the endogenous NMDA receptor antagonist, and the ratio of kynurenic acid/kynurenine were significantly decreased by acute treatment of LPS, which may further strengthen NMDA receptor activation. Since that NMDA activation can exacerbate inflammatory and neurodegenerative process, the enhanced glutamate release and dysregulated kynurenine pathway might constitute a vicious cycle playing a pivotal role in the neuropsychiatric disorders associated with inflammation, such as depression.
- Subjects :
- Lipopolysaccharides
Male
0301 basic medicine
medicine.medical_specialty
Kynurenine pathway
Microdialysis
Immunology
Biology
Hippocampus
Rats, Sprague-Dawley
Food Preferences
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Kynurenic acid
Tandem Mass Spectrometry
Dopamine
Internal medicine
medicine
Animals
Immunology and Allergy
Neurotransmitter
Chromatography, High Pressure Liquid
Kynurenine
Swimming
Analysis of Variance
Neurotransmitter Agents
Glutamate receptor
Immobility Response, Tonic
Rats
030104 developmental biology
Endocrinology
Neurology
chemistry
NMDA receptor
Neurology (clinical)
Serotonin
030217 neurology & neurosurgery
Signal Transduction
medicine.drug
Subjects
Details
- ISSN :
- 01655728
- Database :
- OpenAIRE
- Journal :
- Journal of Neuroimmunology
- Accession number :
- edsair.doi.dedup.....ece063412fb806fa106a2f2d3744f5ff