Metabolic consequences of interleukin-6 challenge in developing neurons and astroglia

Jacquelyn A. Brown, Stacy D. Sherrod, Cody R. Goodwin, Bryson Brewer, Lijie Yang, Krassimira A. Garbett, Deyu Li, John A. Mclean, John P. Wikswo, K. Mirnics

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)183
Number of pages1
JournalJournal of Neuroinflammation
DOIs
Publication statusAccepted/In press - Nov 6 2014

Fingerprint

Astrocytes
Interleukin-6
Neurons
Microfluidics
Autistic Disorder
Schizophrenia
Central Nervous System
Mothers
Glycerophospholipids
Technology
Kynurenine
Brain
Gravitation
Brain Diseases
Cell Size
Tryptophan
Liquid Chromatography
Causality
Nervous System
Interleukin-2

Keywords

  • glycerophospholipid
  • immune activation
  • interleukin
  • kynurenine
  • metabolomics
  • microfluidics
  • ultra-performance liquid chromatography - ion mobility - mass spectrometry

ASJC Scopus subject areas

  • Neuroscience(all)
  • Cellular and Molecular Neuroscience
  • Neurology
  • Immunology

Cite this

Metabolic consequences of interleukin-6 challenge in developing neurons and astroglia. / Brown, Jacquelyn A.; Sherrod, Stacy D.; Goodwin, Cody R.; Brewer, Bryson; Yang, Lijie; Garbett, Krassimira A.; Li, Deyu; Mclean, John A.; Wikswo, John P.; Mirnics, K.

In: Journal of Neuroinflammation, 06.11.2014, p. 183.

Research output: Contribution to journalArticle

Brown, JA, Sherrod, SD, Goodwin, CR, Brewer, B, Yang, L, Garbett, KA, Li, D, Mclean, JA, Wikswo, JP & Mirnics, K 2014, 'Metabolic consequences of interleukin-6 challenge in developing neurons and astroglia', Journal of Neuroinflammation, pp. 183. https://doi.org/10.1186/s12974-014-0183-6
Brown, Jacquelyn A. ; Sherrod, Stacy D. ; Goodwin, Cody R. ; Brewer, Bryson ; Yang, Lijie ; Garbett, Krassimira A. ; Li, Deyu ; Mclean, John A. ; Wikswo, John P. ; Mirnics, K. / Metabolic consequences of interleukin-6 challenge in developing neurons and astroglia. In: Journal of Neuroinflammation. 2014 ; pp. 183.
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AU - Goodwin, Cody R.

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AU - Yang, Lijie

AU - Garbett, Krassimira A.

AU - Li, Deyu

AU - Mclean, John A.

AU - Wikswo, John P.

AU - Mirnics, K.

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