Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hypothalamic dysfunction is a key factor in depression; increasing evidence highlights neuroinflammation abnormalities as well as imbalances in neurotransmitters and the purinergic system in the pathophysiology of depression. However, little is known about the metabolomic changes in the hypothalamus of depressed patients with neuroinflammation. Herein, taking advantage of the well-established lipopolysaccharide (LPS)-induced depression mouse model, we measured metabolic changes in the hypothalamus using gas chromatography-mass spectrometry (GC-MS). Sucrose preference test (SPT), open field test (OFT), forced swimming test (FST), and tail suspension test (TST) were conducted to assess our depressive model. To better understand the metabolic disturbances occurring in the hypothalamus of depressed mice, multivariate statistics were applied to analyse the clinical significance of differentially expressed metabolites in the hypothalamus of mice with LPS-induced depression. Bioinformatic analysis was conducted to detect potential relationships among the changed metabolites. The data confirmed that mice with LPS-induced depression were good mimics of depression patients in some characteristic symptoms such as decreased sucrose intake and increased immobility. In our study, 27 differentially expressed metabolites were identified in the hypothalamus of mice with LPS-induced depression. Herein, seventeen of these metabolites decreased, whereas 10 metabolites increased. These molecular changes were closely related to perturbations in the amino acid and purine metabolisms. Our data indicate that dysfunction of amino acid and purine metabolisms is one of main characteristics of inflammation-mediated depression. These results provide new insights into the mechanisms underlying depression, which may shed some light on the role of the hypothalamus in the pathogenesis of inflammation-mediated depression.
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PMID:Imbalance in amino acid and purine metabolisms at the hypothalamus in inflammation-associated depression by GC-MS. 2916 Mar 27

Hypothalamic dysfunction is a key pathological factor in inflammation-associated depression. In the present study, isobaric tags for relative-absolute quantitation (iTRAQ) combined with mass spectrometry and gas chromatography-mass spectrometry (GC-MS) were employed to detect the proteomes and metabolomes in the hypothalamus of the lipopolysaccharide (LPS)-induced depression mouse, respectively. A total of 187 proteins and 27 metabolites were differentially expressed compared with the control group. Following the integration of bi-omics data, pertinent pathways and molecular interaction networks were further identified. The results indicated altered molecules were clustered into Ephrin receptor signaling, glutamatergic transmission, and inflammation-related signaling included the LXR/RXR activation, FXR/RXR activation, and acute phase response signaling. First discovered in the hypothalamus, Ephrin receptor signaling regulates N-methyl-D-aspartate receptor (NMDAR)-predominant glutamatergic transmission, and further acted on AKT signaling that contributed to changes in hypothalamic neuroplasticity. Ephrin type-B receptor 2 (EPHB2), a transmembrane receptor protein in Ephrin receptor signaling, was significantly elevated and interacted with the accumulated NMDAR subunit GluN2A in the hypothalamus. Additionally, molecules involved in synaptic plasticity regulation, such as hypothalamic postsynaptic density protein-95 (PSD-95), p-AKT and brain-derived neurotrophic factor (BDNF), were significantly altered in the LPS-induced depressed group. It might be an underlying pathogenesis that the EPHB2-GluN2A-AKT cascade regulates synaptic plasticity in depression. EPHB2 can be a potential therapeutic target in the correction of glutamatergic transmission dysfunction. In summary, our findings point to the previously undiscovered molecular underpinnings of the pathophysiology in the hypothalamus of inflammation-associated depression and offer potential targets to develop antidepressants.
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PMID:Perturbation of Ephrin Receptor Signaling and Glutamatergic Transmission in the Hypothalamus in Depression Using Proteomics Integrated With Metabolomics. 3192 May 18