NeuroMolecular Medicine

, Volume 14, Issue 4, pp 349–361

Lipidomic Profiling of Phosphocholine Containing Brain Lipids in Mice with Sensorimotor Deficits and Anxiety-Like Features After Exposure to Gulf War Agents

Authors

    • Roskamp Institute
  • James E. Evans
    • Roskamp Institute
  • Alex Bishop
    • Roskamp Institute
  • Jon M. Reed
    • Roskamp Institute
  • Gogce Crynen
    • Roskamp Institute
  • John Phillips
    • Roskamp Institute
  • Robert Pelot
    • Roskamp Institute
  • Myles A. Mullan
    • Roskamp Institute
  • Austin Ferro
    • Roskamp Institute
  • Christopher M. Mullan
    • Roskamp Institute
  • Michael J. Mullan
    • Roskamp Institute
  • Ghania Ait-Ghezala
    • Roskamp Institute
  • Fiona C. Crawford
    • Roskamp Institute
Original Paper

DOI: 10.1007/s12017-012-8192-z

Cite this article as:
Abdullah, L., Evans, J.E., Bishop, A. et al. Neuromol Med (2012) 14: 349. doi:10.1007/s12017-012-8192-z

Abstract

The central nervous system (CNS)-based symptoms of Gulf War Illness (GWI) include motor dysfunction, anxiety, and cognitive impairment. Gulf War (GW) agents, such as pyridostigmine bromide (PB), permethrin (PER), N,N-diethyl-meta-toluamide (DEET), and stress, are among the contributory factors to the pathobiology of GWI. This study characterizes disturbances in phosphocholine-containing lipids that accompany neurobehavioral and neuropathological features associated with GW agent exposure. Exposed mice received PB orally, dermal application of PER and DEET and restraint stress daily for 28 days, while controls received vehicle during this period. Neurobehavioral studies included the rotarod, open field, and Morris water maze tests. Histopathological assessments included glial fibrillary acid protein, CD45, and Nissl staining. Liquid chromatography/mass spectrometry with source collision-induced dissociation in negative and positive ionization scanning modes was performed to characterize brain phosphatidylcholine (PC) and sphingomyelin (SM). A significant increase in ether containing PC (ePC34:0, ePC36:2, and ePC36:1) or long-chain fatty acid-containing PC (38:1, 40:4, 40:2) was observed in exposed mice compared with controls. Among differentially expressed PCs, levels of those with monounsaturated fatty acids were more affected than those with saturated and polyunsaturated fatty acids. Sensorimotor deficits and anxiety, together with an increase in astrocytosis, were observed in exposed mice compared with controls. These lipid changes suggest that alterations in peroxisomal pathways and stearoyl-CoA desaturase activity accompany neurobehavioral and neuropathological changes after GW agent exposure and represent possible treatment targets for the CNS symptoms of GWI.

Keywords

Gulf War IllnessLipidomicsPhosphatidylcholineSphingomyelinPyridostigmine bromidePermethrinN,N-diethyl-meta-toluamide and stress

Copyright information

© Springer Science+Business Media, LLC 2012