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Metabolic consequences of interleukin-6 challenge in developing neurons and astroglia
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نویسنده
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brown j.a. ,sherrod s.d. ,goodwin c.r. ,brewer b. ,yang l. ,garbett k.a. ,li d. ,mclean j.a. ,wikswo j.p. ,mirnics k.
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منبع
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journal of neuroinflammation - 2014 - دوره : 11 - شماره : 0
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چکیده
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Background: maternal immune activation and subsequent interleukin-6 (il-6) induction disrupt normal brain development and predispose the offspring to developing autism and schizophrenia. while several proteins have been identified as having some link to these developmental disorders,their prevalence is still small and their causative role,if any,is not well understood. however,understanding the metabolic consequences of environmental predisposing factors could shed light on disorders such as autism and schizophrenia. methods: to gain a better understanding of the metabolic consequences of il-6 exposure on developing central nervous system (cns) cells,we separately exposed developing neuron and astroglia cultures to il-6 for 2 hours while collecting effluent from our gravity-fed microfluidic chambers. by coupling microfluidic technologies to ultra-performance liquid chromatography-ion mobility-mass spectrometry (uplc-im-ms),we were able to characterize the metabolic response of these cns cells to a narrow window of il-6 exposure. results: our results revealed that 1) the use of this technology,due to its superb media volume:cell volume ratio,is ideally suited for analysis of cell-type-specific exometabolome signatures; 2) developing neurons have low secretory activity at baseline,while astroglia show strong metabolic activity; 3) both neurons and astroglia respond to il-6 exposure in a cell type-specific fashion; 4) the astroglial response to il-6 stimulation is predominantly characterized by increased levels of metabolites,while neurons mostly depress their metabolic activity; and 5) disturbances in glycerophospholipid metabolism and tryptophan/kynurenine metabolite secretion are two putative mechanisms by which il-6 affects the developing nervous system. conclusions: our findings are potentially critical for understanding the mechanism by which il-6 disrupts brain function,and they provide information about the molecular cascade that links maternal immune activation to developmental brain disorders. © 2014 brown et al.
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کلیدواژه
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Glycerophospholipid; Immune activation; Interleukin; Kynurenine; Metabolomics; Microfluidics; Ultra-performance liquid chromatography - ion mobility - mass spectrometry
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آدرس
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department of psychiatry,vanderbilt university,465 21st avenue south,nashville,tn 37232,united states,vanderbilt institute for integrative biosystems research and education,6809 stevenson center,vanderbilt university,nashville,tn 37235, United States, vanderbilt institute for integrative biosystems research and education,6809 stevenson center,vanderbilt university,nashville,tn 37235,united states,department of physics and astronomy,6301 stevenson center,vanderbilt university,nashville,tn 37235, United States, vanderbilt institute for integrative biosystems research and education,6809 stevenson center,vanderbilt university,nashville,tn 37235,united states,department of chemistry,5421 stevenson center,vanderbilt university,nashville,tn 37235, United States, department of mechanical engineering,vanderbilt university,333 olin hall,nashville,tn 37235, United States, department of mechanical engineering,vanderbilt university,333 olin hall,nashville,tn 37235, United States, department of psychiatry,vanderbilt university,465 21st avenue south,nashville,tn 37232, United States, vanderbilt institute for integrative biosystems research and education,6809 stevenson center,vanderbilt university,nashville,tn 37235,united states,department of mechanical engineering,vanderbilt university,333 olin hall,nashville,tn 37235, United States, vanderbilt institute for integrative biosystems research and education,6809 stevenson center,vanderbilt university,nashville,tn 37235,united states,department of chemistry,5421 stevenson center,vanderbilt university,nashville,tn 37235, United States, vanderbilt institute for integrative biosystems research and education,6809 stevenson center,vanderbilt university,nashville,tn 37235,united states,department of physics and astronomy,6301 stevenson center,vanderbilt university,nashville,tn 37235,united states,department of biomedical engineering,5824 stevenson center,vanderbilt university,nashville,tn 37235,united states,department of molecular physiology and biophysics,vanderbilt university,702 light hall,nashville,tn 37232, United States, department of psychiatry,vanderbilt university,465 21st avenue south,nashville,tn 37232,united states,vanderbilt institute for integrative biosystems research and education,6809 stevenson center,vanderbilt university,nashville,tn 37235,united states,vanderbilt kennedy center for research on human development,vanderbilt university,110 magnolia circle,nashville,tn 37203,united states,department of psychiatry,university of szeged,szeged,6725, Hungary
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Authors
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