Proteomic analysis of demyelinated and remyelinating brain tissue following dietary cuprizone administration.
Cuprizone intoxication is a commonly used model of demyelination that allows the temporal separation of demyelination and remyelination. The underlying biochemical alterations leading to demyelination, using this model, remain unclear and may be multifold. Analysis of proteomic changes within the brains of cuprizone-exposed animals may help elucidate key cellular processes. In the current study, we report the results of the liquid chromatography tandem mass spectrometry analysis of total protein from the brain hemispheres of control and toxin-exposed mice at 6 weeks of exposure and after 3 and 6 weeks of recovery to identify protein changes during the remyelination phase. We found that at 6 weeks of cuprizone exposure, myelin proteins were reduced compared to controls and increased throughout the course of recovery, as expected. In contrast, other protein groups, such as proteins related to mitochondrial function, were increased at 6 weeks of treatment compared to untreated controls and returned toward control levels following withdrawal of toxin. These results suggest that a global proteomic analysis of the brain tissue of cuprizone-treated mice can identify changes related to the demyelination/remyelination process.
Werner
Sean R
SR
Biotechnology Discovery Research, Eli Lilly and Company, Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, IN 46285, USA. sean.werner@cookmedical.com
Saha
Joy K
JK
Broderick
Carol L
CL
Zhen
Eugene Y
EY
Higgs
Richard E
RE
Duffin
Kevin L
KL
Smith
Rosamund C
RC
D000284:Administration, Oral; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D003471:Cuprizone / Q000633:toxicity*; D003711:Demyelinating Diseases / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D005526:Food, Formulated / Q000009:adverse effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008996:Monoamine Oxidase Inhibitors / Q000633:toxicity; D009413:Nerve Fibers, Myelinated / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D009416:Nerve Regeneration / Q000187:drug effects / Q000502:physiology*; D009498:Neurotoxins / Q000633:toxicity; D040901:Proteomics / Q000379:methods*; D020127:Recovery of Function / Q000502:physiology
D008996:Monoamine Oxidase Inhibitors; D009498:Neurotoxins; D003471:Cuprizone
Physiol Rev. 2000 Jan;80(1):315-60
10617771
Biochem Biophys Res Commun. 2005 Jul 1;332(2):542-9
15896715
Front Biosci. 2008 Jan 01;13:3116-26
17981781
Physiol Res. 2006;55 Suppl 2:S27-41
17298220
J Neuroimmunol. 2007 Aug;188(1-2):1-12
17493689
Nature. 2008 Feb 28;451(7182):1076-81
18278032
J Proteome Res. 2005 Jul-Aug;4(4):1442-50
16083298
Am J Med Genet. 1987 Jan;26(1):207-15
3812564
Neurosci Lett. 2009 Apr 3;453(2):120-5
19356606
J Neurol Sci. 1999 Oct 15;168(2):116-20
10526193
Curr Top Microbiol Immunol. 2008;318:1-17
18219812
Glia. 2006 Apr 1;53(5):529-37
16374777
J Bioenerg Biomembr. 1990 Oct;22(5):663-77
2249978
J Am Soc Mass Spectrom. 1994 Nov;5(11):976-89
24226387
Toxicol Lett. 2007 Mar 30;169(3):205-13
17317045
Am Fam Physician. 2004 May 15;69(10):2405-10
15168961
Brain Pathol. 2007 Apr;17(2):219-29
17388953
Neurology. 1990 Mar;40(3 Pt 1):487-91
2314592
Neurogenetics. 2001 Jul;3(3):119-25
11523562
Brain Pathol. 2001 Jan;11(1):107-16
11145196
Am J Pathol. 2008 Apr;172(4):1053-61
18349131
J Proteome Res. 2008 Jan;7(1):29-34
18067246
Rapid Commun Mass Spectrom. 2003;17(20):2310-6
14558131
Proc Natl Acad Sci U S A. 2004 Nov 16;101(46):16363-8
15534218
Neuropathol Appl Neurobiol. 2008 Feb;34(1):105-14
17961136
Cell Metab. 2007 Jan;5(1):9-20
17189203
Cell Mol Life Sci. 2005 Jul;62(13):1502-13
15971002
Mol Cell Neurosci. 2000 Oct;16(4):338-49
11085872
J Mol Neurosci. 2006;28(1):3-15
16632872
Exp Neurol. 2008 Apr;210(2):308-21
18096162
J Nutr. 1999 Jul;129(7):1251-60
10395584
Med Hypotheses. 2005;64(4):669-77
15694681
Acta Neuropathol. 2009 Dec;118(6):723-36
19763593
Curr Top Microbiol Immunol. 2008;318:213-39
18219820
Annu Rev Med. 2008;59:131-46
17892433
J Proteome Res. 2007 Jul;6(7):2565-75
17571869
J Neurocytol. 1972 Dec;1(4):413-26
8530973
Cerebellum. 2009 Sep;8(3):163-74
19259754
J Proteome Res. 2008 Jan;7(1):40-4
18052118
J Neurosci. 2003 Oct 29;23(30):9824-32
14586011
Mol Cell Neurosci. 1998 Nov;12(4-5):220-7
9828087
Dalton Trans. 2007 Jun 7;(21):2112-4
17514330
Mult Scler. 2004 Jun;10(3):245-60
15222687
Mult Scler. 2007 Aug;13(7):840-9
17881397
Brain Pathol. 2003 Jul;13(3):329-39
12946022
Nat Med. 2005 Sep;11(9):966-72
16086023
J Neurol Sci. 1988 Apr;84(2-3):223-37
2837540
J Cell Biol. 2008 Dec 1;183(5):909-21
19047465
Curr Top Microbiol Immunol. 2008;318:19-43
18219813
J Neurosci Res. 2000 Aug 1;61(3):251-62
10900072
Brain Res. 2009 Aug 4;1283:127-38
19524552
Am J Med Genet. 2002 Dec 15;113(4):371-4
12457410
J Neurochem. 2002 Jul;82(1):126-36
12091473
J Proteome Res. 2007 May;6(5):1758-67
17397207