OpenLB
Open Library of Bioscience
Advanced Search
Neuromolecular medicine
Dec, 2011;13 (4): 275-88.

Proteomic CNS profile of delayed cognitive impairment in mice exposed to Gulf War agents.

Laila Abdullah, Gogce Crynen, Jon Reed, Alex Bishop, John Phillips, Scott Ferguson, Benoit Mouzon, Myles Mullan, Venkatarajan Mathura, Michael Mullan, Ghania Ait-Ghezala, Fiona Crawford
Author Information
  1. Laila Abdullah: Roskamp Institute, 2040 Whitfield Ave, Sarasota, FL, 34243, USA. labdullah@rfdn.org
PMID: 21986894 DOI: 10.1007/s12017-011-8160-z

Abstract

Gulf War Illness (GWI) is a chronic multisymptom condition with a central nervous system (CNS) component, for which there is no treatment available. It is now believed that the combined exposure to Gulf War (GW) agents, including pyridostigmine bromide (PB) and pesticides, such as permethrin (PER), was a key contributor to the etiology of GWI. In this study, a proteomic approach was used to characterize the biomolecular disturbances that accompany neurobehavioral and neuropathological changes associated with combined exposure to PB and PER. Mice acutely exposed to PB and PER over 10 days showed an increase in anxiety-like behavior, psychomotor problems and delayed cognitive impairment compared to control mice that received vehicle only. Proteomic analysis showed changes in proteins associated with lipid metabolism and molecular transport in the brains of GW agent-exposed mice compared to controls. Proteins associated with the endocrine and immune systems were also altered, and dysfunction of these systems is a prominent feature of GWI. The presence of astrogliosis in the GW agent-exposed mice compared to control mice further suggests an immune system imbalance, as is observed in GWI. These studies provide a broad perspective of the molecular disturbances driving the late pathology of this complex illness. Evaluation of the potential role of these biological functions in GWI will be useful in identifying molecular pathways that can be targeted for the development of novel therapeutics against GWI.

References

  1. Vet Hum Toxicol. 1997 Aug;39(4):214-9 [PMID: 9251170]
  2. J Toxicol Environ Health A. 2004 Jan 23;67(2):163-92 [PMID: 14675905]
  3. Psychol Med. 2002 Nov;32(8):1357-70 [PMID: 12455934]
  4. Nat Rev Neurosci. 2009 Sep;10(9):635-46 [PMID: 19693028]
  5. Pharmacol Biochem Behav. 2004 Feb;77(2):253-62 [PMID: 14751452]
  6. Immunopharmacol Immunotoxicol. 2004 Feb;26(1):1-15 [PMID: 15106728]
  7. J Neurol Sci. 2008 Apr 15;267(1-2):3-16 [PMID: 17935736]
  8. Horm Res. 2005;64 Suppl 3:100-8 [PMID: 16439852]
  9. Toxicol Ind Health. 2009 Feb;25(1):25-39 [PMID: 19318502]
  10. Mol Neurobiol. 2010 Jun;41(2-3):115-28 [PMID: 20195797]
  11. Neuroscience. 2011 Mar 10;176:237-53 [PMID: 21185910]
  12. J Neurol Sci. 2008 Mar 15;266(1-2):20-4 [PMID: 17869272]
  13. J Proteome Res. 2008 Aug;7(8):3091-101 [PMID: 18578521]
  14. Mil Med. 1997 Apr;162(4):249-51 [PMID: 9110548]
  15. Behav Brain Res. 2009 Feb 11;197(2):301-10 [PMID: 18793677]
  16. J Int Neuropsychol Soc. 2009 Sep;15(5):717-29 [PMID: 19640317]
  17. J Psychopharmacol. 2007 Mar;21(2):134-5 [PMID: 17329288]
  18. J Photochem Photobiol B. 2005 Jan 14;78(1):29-34 [PMID: 15629246]
  19. Mol Cell Proteomics. 2008 Sep;7(9):1702-13 [PMID: 18511480]
  20. Int J Toxicol. 2003 Sep-Oct;22(5):359-70 [PMID: 14555407]
  21. Psychol Rep. 2002 Jun;90(3 Pt 1):707-21 [PMID: 12090498]
  22. Philos Trans R Soc Lond B Biol Sci. 2006 Apr 29;361(1468):593-604 [PMID: 16687264]
  23. Brain Res Bull. 2002 Jan 1;57(1):17-26 [PMID: 11827733]
  24. Inflamm Res. 1998;47 Suppl 1:S11-2 [PMID: 9561393]
  25. Bull Environ Contam Toxicol. 1995 May;54(5):768-74 [PMID: 7780222]
  26. BMC Med Genomics. 2009 Mar 05;2:12 [PMID: 19265525]
  27. Am J Med. 2004 Oct 1;117(7):469-78 [PMID: 15464703]
  28. Tohoku J Exp Med. 2008 Apr;214(4):303-10 [PMID: 18441505]
  29. Comp Biochem Physiol C Comp Pharmacol Toxicol. 1987;86(2):349-52 [PMID: 2882930]
  30. Biochemistry. 2005 Apr 26;44(16):6350-60 [PMID: 15835924]
  31. J Neurosci. 2004 Mar 3;24(9):2143-55 [PMID: 14999065]
  32. Neurosci Biobehav Rev. 2001 May;25(3):205-18 [PMID: 11378177]
  33. Neurotoxicology. 2006 Jul;27(4):508-19 [PMID: 16516970]
  34. J Neurol Neurosurg Psychiatry. 1983 Oct;46(10):929-35 [PMID: 6644317]
  35. Brain Res. 2004 May 29;1009(1-2):189-94 [PMID: 15120596]
  36. Clin Diagn Lab Immunol. 1999 Jan;6(1):6-13 [PMID: 9874656]
  37. Pharmacol Biochem Behav. 1999 Jul;63(3):401-6 [PMID: 10418780]
  38. Pharmacol Ther. 2006 Jul;111(1):174-93 [PMID: 16324748]
  39. Learn Mem. 1997 Jan-Feb;3(5):402-13 [PMID: 10456107]
  40. Vet Hum Toxicol. 2000 Apr;42(2):72-6 [PMID: 10750169]
  41. J Clin Immunol. 2004 Jan;24(1):66-73 [PMID: 14997036]
  42. J Neurosci. 2002 Mar 1;22(5):1709-17 [PMID: 11880500]
  43. J Appl Toxicol. 2009 Jul;29(5):386-94 [PMID: 19283689]
  44. J Alzheimers Dis. 2010;22(4):1281-8 [PMID: 20930282]
  45. Psychiatry Res. 2005 Jul 30;139(2):89-99 [PMID: 15967648]
  46. J Proteome Res. 2008 Feb;7(2):731-40 [PMID: 18183947]
  47. Nat Med. 1996 Dec;2(12):1382-5 [PMID: 8946841]
  48. Neuroscience. 2009 Apr 10;159(4):1349-62 [PMID: 19409232]
  49. Food Chem Toxicol. 2001 Feb;39(2):133-9 [PMID: 11267706]
  50. Ann N Y Acad Sci. 2006 Jul;1071:448-53 [PMID: 16891596]
  51. J Occup Environ Med. 1998 Jun;40(6):520-8 [PMID: 9636932]
  52. J Neurosci. 2002 Jan 15;22(2):515-22 [PMID: 11784797]
  53. Yakugaku Zasshi. 2009 Feb;129(2):191-5 [PMID: 19182446]
  54. Am J Ind Med. 2001 Jul;40(1):42-54 [PMID: 11439396]
  55. Am J Epidemiol. 2000 Nov 15;152(10):992-1002 [PMID: 11092441]
  56. Neurobiol Dis. 2002 Aug;10(3):306-26 [PMID: 12270692]
  57. Am J Trop Med Hyg. 1999 May;60(5):758-66 [PMID: 10344649]
  58. Brain. 2006 Oct;129(Pt 10):2761-72 [PMID: 16825202]

MeSH Term

Acute Disease
Animals
Anxiety
Biological Transport
Central Nervous System
Cognition Disorders
Endocrine System
Enzyme Inhibitors
Immune System
Insecticides
Lipid Metabolism
Male
Mice
Permethrin
Persian Gulf Syndrome
Proteomics
Psychomotor Performance
Pyridostigmine Bromide
Veterans

Chemicals

Enzyme Inhibitors
Insecticides
Permethrin
Pyridostigmine Bromide
Journal Article Research Support, U.S. Gov't, Non-P.H.S.
Article has an altmetric score of 13

Word Cloud

Created with Highcharts 10.0.0GWImiceGulfWarGWPBPERassociatedcomparedmolecularsystemCNScombinedexposureagentsdisturbanceschangesexposedshoweddelayedcognitiveimpairmentcontrolProteomicagent-exposedimmunesystemsIllnesschronicmultisymptomconditioncentralnervouscomponenttreatmentavailablenowbelievedincludingpyridostigminebromidepesticidespermethrinkeycontributoretiologystudyproteomicapproachusedcharacterizebiomolecularaccompanyneurobehavioralneuropathologicalMiceacutely10daysincreaseanxiety-likebehaviorpsychomotorproblemsreceivedvehicleanalysisproteinslipidmetabolismtransportbrainscontrolsProteinsendocrinealsoaltereddysfunctionprominentfeaturepresenceastrogliosissuggestsimbalanceobservedstudiesprovidebroadperspectivedrivinglatepathologycomplexillnessEvaluationpotentialrolebiologicalfunctionswillusefulidentifyingpathwayscantargeteddevelopmentnoveltherapeuticsprofile

Similar Articles

Cited By