title: Quantitative profiling of neurotransmitter abnormalities in the hippocampus of rats treated with lipopolysaccharide: Focusing on kynurenine pathway and implications for depression.
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 (3mg/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 (500μg/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.
authors.affiliation: Institute of Clinical Pharmacy & Pharmacology, Jining First People's Hospital, Jining Medical University, Jining 272000, China.
authors.forename: Yujin
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Department of pharmacy, Second Xiangya Hospital, Central South University, Changsha 410010, China.
authors.forename: Hualin
authors.initials: H
authors.lastname: Cai
authors.affiliation: Department of pharmacy, Second Xiangya Hospital, Central South University, Changsha 410010, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Chen
authors.affiliation: Institute of Clinical Pharmacy & Pharmacology, Jining First People's Hospital, Jining Medical University, Jining 272000, China.
authors.forename: Donglou
authors.initials: D
authors.lastname: Liang
authors.affiliation: Institute of Clinical Pharmacy & Pharmacology, Jining First People's Hospital, Jining Medical University, Jining 272000, China.
authors.forename: Ranyao
authors.initials: R
authors.lastname: Yang
authors.affiliation: Institute of Clinical Pharmacy & Pharmacology, Jining First People's Hospital, Jining Medical University, Jining 272000, China. Electronic address: ruilidang@gmail.com.
authors.forename: Ruili
authors.initials: R
authors.lastname: Dang
authors.affiliation: Institute of Clinical Pharmacy & Pharmacology, Jining First People's Hospital, Jining Medical University, Jining 272000, China. Electronic address: jiangpeicsu@sina.com.
authors.forename: Pei
authors.initials: P
authors.lastname: Jiang
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D005518:Food Preferences / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects*; D046353:Immobility Response, Tonic / Q000187:drug effects; D007737:Kynurenine / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D017551:Microdialysis; D018377:Neurotransmitter Agents / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*; D013550:Swimming / Q000523:psychology; D053719:Tandem Mass Spectrometry
chemical_list: D008070:Lipopolysaccharides; D018377:Neurotransmitter Agents; D007737:Kynurenine
keywords: Depression; Kynurenine pathway; Lipopolysaccharide; Neurotransmitters