Microglial ablation and lipopolysaccharide preconditioning affects pilocarpine-induced seizures in mice.
Activated microglia have been associated with neurodegeneration in patients and in animal models of Temporal Lobe Epilepsy (TLE), however their precise functions as neurotoxic or neuroprotective is a topic of significant investigation. To explore this, we examined the effects of pilocarpine-induced seizures in transgenic mice where microglia/macrophages were conditionally ablated. We found that unilateral ablation of microglia from the dorsal hippocampus did not alter acute seizure sensitivity. However, when this procedure was coupled with lipopolysaccharide (LPS) preconditioning (1 mg/kg given 24 h prior to acute seizure), we observed a significant pro-convulsant phenomenon. This effect was associated with lower metabolic activation in the ipsilateral hippocampus during acute seizures, and could be attributed to activity in the mossy fiber pathway. These findings reveal that preconditioning with LPS 24 h prior to seizure induction may have a protective effect which is abolished by unilateral hippocampal microglia/macrophage ablation.
Mirrione
Martine M
MM
Department of Pharmacological Sciences, Molecular and Cellular Pharmacology, Stony Brook University, Stony Brook, NY 11794-8651, USA.
Konomos
Dorothy K
DK
Gravanis
Iordanis
I
Dewey
Stephen L
SL
Aguzzi
Adriano
A
Heppner
Frank L
FL
Tsirka
Stella E
SE
D000208:Acute Disease; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D004827:Epilepsy / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D010862:Pilocarpine / Q000008:administration & dosage*
D008070:Lipopolysaccharides; D010862:Pilocarpine
J Neurosci Methods. 2006 Sep 15;155(2):272-84
16519945
J Neurosci. 2008 Nov 19;28(47):12477-88
19020040
Neuroscience. 2009 Sep 15;162(4):972-9
19477240
J Immunol. 2009 Aug 1;183(3):2068-78
19596989
Med Microbiol Immunol. 2002 Mar;190(4):173-8
12005330
J Cell Biol. 2000 Mar 20;148(6):1295-304
10725341
Neurobiol Dis. 2007 Apr;26(1):66-77
17239605
Proc Natl Acad Sci U S A. 1997 Apr 15;94(8):4103-8
9108112
J Neuroimmune Pharmacol. 2009 Dec;4(4):371-9
19680817
Neurosci Biobehav Rev. 1990 Winter;14(4):511-7
2287490
J Neurosci. 1996 Apr 15;16(8):2508-21
8786427
Eur J Neurosci. 2006 Aug;24(4):1063-70
16925588
Epilepsia. 2009 Jan;50(1):88-98
18727682
Epilepsia. 2003 Feb;44(2):193-9
12558573
Nat Neurosci. 2008 Jan;11(1):109-17
18066056
Epilepsia. 2005 Apr;46(4):573-6
15816953
Neuroreport. 1996 Apr 26;7(6):1125-9
8817515
Epilepsia. 2006 Jan;47(1):41-6
16417530
Brain. 2009 Sep;132(Pt 9):2478-86
19567702
Glia. 2005 Jan 15;49(2):177-83
15494978
J Cell Sci. 1999 Nov;112 ( Pt 22):4007-16
10547361
Proc Natl Acad Sci U S A. 2000 Oct 10;97(21):11534-9
11016948
Glia. 2006 Sep;54(4):258-71
16845674
Glia. 2006 Oct;54(5):358-68
16886201
Development. 1994 Nov;120(11):3173-83
7720560
PLoS One. 2009 Jun 02;4(6):e5759
19503612
J Neurosci. 2003 Apr 15;23(8):3234-42
12716930
Neuroscience. 2006 May 12;139(2):475-83
16473474
J Neurosci. 2005 Feb 16;25(7):1797-805
15716416
Proc Natl Acad Sci U S A. 2008 Nov 4;105(44):17151-6
18955701
Nature. 2006 Apr 20;440(7087):1054-9
16547515
Neuroimage. 2007 Oct 15;38(1):34-42
17707126
Neurobiol Dis. 2008 Jan;29(1):142-60
17931873
J Neurosci Res. 2008 May 15;86(7):1608-14
18189316
Neurosci Lett. 1996 Oct 11;217(1):29-32
8905732
Epilepsia. 2002;43 Suppl 9:39-43
12383279
Glia. 1998 Apr;22(4):401-7
9517572
Neurochem Res. 2010 Feb;35(2):262-72
19728087
J Neurosci. 2002 May 1;22(9):3352-8
11978811
Brain Res Rev. 2007 Aug;55(1):89-96
17509690
Epilepsy Res. 2006 Oct;71(2-3):181-7
16870400
J Neurocytol. 2002 Sep-Nov;31(8-9):681-92
14501207
J Neurosci. 2009 Aug 5;29(31):9839-49
19657036
Nat Med. 2005 Feb;11(2):146-52
15665833
Epilepsia. 2008;49 Suppl 2:33-41
18226170
J Neurosci Res. 2001 Aug 15;65(4):322-31
11494368
J Neurosci Res. 2010 Feb 15;88(3):519-29
19774666
J Neurosci Res. 1997 Dec 15;50(6):1023-9
9452017
Prog Brain Res. 2007;163:285-97
17765725
Ann Neurol. 2005 Jun;57(6):804-12
15852477
Neuroscience. 2003;122(4):1073-80
14643773
Mol Pharmacol. 1999 Aug;56(2):339-47
10419553
Exp Neurol. 2005 Dec;196(2):316-31
16342370
J Neurosci. 2009 Apr 1;29(13):3974-80
19339593
Prog Neurobiol. 1999 Apr;57(6):563-81
10221782
Neuroscience. 2009 Feb 6;158(3):1007-20
18809468
Neurology. 2009 Sep 29;73(13):1033-40
19710404
Neurobiol Dis. 2004 Jul;16(2):321-34
15193289
Eur J Paediatr Neurol. 2005;9(1):29-42
15701565
Exp Neurol. 2003 Jul;182(1):21-34
12821374
J R Soc Interface. 2009 Aug 6;6(37):655-68
18986963
Stroke. 2004 Nov;35(11):2576-81
15375302
Epilepsy Res. 2003 Dec;57(2-3):175-80
15013059
Nature. 1995 Sep 28;377(6547):340-4
7566088
Exp Neurol. 2006 Oct;201(2):416-27
16793040
Curr Biol. 1998 Jan 1;8(1):19-25
9427623
Neuroscience. 2005;135(4):1203-15
16165303
Epilepsy Res. 2009 Oct;86(2-3):124-30
19535227
Arch Neurol. 2001 Jun;58(6):933-9
11405808
Int Rev Neurobiol. 2001;45:237-52
11130901
J Physiol. 2008 Jan 15;586(2):427-39
17991695
Epilepsia. 2006 Jul;47(7):1160-8
16886979
Brain Res. 1984 Nov 12;321(2):237-53
6498517
Neurosci Lett. 1995 May 19;191(1-2):27-30
7659283
Epilepsia. 2007;48 Suppl 4:56-64
17767576
Neuroscience. 2004;129(4):1045-56
15561419
Epilepsia. 2010 Mar;51(3):415-22
19694792
Ann Neurol. 2003 Nov;54(5):655-64
14595655
Neurosci Lett. 2001 Jul 20;307(3):171-4
11438391
Science. 2003 Dec 5;302(5651):1760-5
14615545
J Neurosci Res. 1998 Oct 1;54(1):117-22
9778155
Exp Neurol. 2009 Nov;220(1):1-4
19646437
J Immunol. 2000 May 15;164(10):5430-8
10799909
J Cereb Blood Flow Metab. 2009 Jun;29(6):1216-25
19352400
Science. 2002 Mar 22;295(5563):2282-5
11910117
Brain. 2007 Feb;130(Pt 2):521-34
17124188
Synapse. 2006 Feb;59(2):119-21
16320304
Epilepsy Res. 2002 Apr;49(2):109-20
12049799
Epilepsia. 2002 Jul;43(7):703-10
12102672
Behav Brain Res. 1983 Mar;7(3):361-70
6132610
Acta Neurol Scand. 2007 Apr;115(4 Suppl):16-20
17362271
J Neurochem. 2005 Mar;92(5):997-1009
15715651
Nat Biotechnol. 2000 Jun;18(6):655-60
10835605
J Neurosci. 2007 Feb 14;27(7):1738-45
17301181
Brain Res. 1972 Nov 27;47(1):262-8
4641271
Rev Med Suisse Romande. 2000 Sep;120(9):739-42
11094539
Trends Neurosci. 2006 Feb;29(2):68-74
16406093
J Neurosci. 1999 Jun 15;19(12):5054-65
10366638
Proc Natl Acad Sci U S A. 2003 Nov 11;100(23):13632-7
14581618
Behav Brain Res. 1983 Sep;9(3):315-35
6639740
Brain Res Mol Brain Res. 2000 Feb 22;75(2):248-58
10686345
Mol Psychiatry. 1996 Dec;1(6):445-52
9154245
Exp Neurol. 2009 May;217(1):205-9
19236862
Life Sci. 2006 May 30;79(1):1-7
16434059
Glia. 2005 Aug 1;51(2):111-20
15789431
Epilepsia. 2007;48 Suppl 4:82-9
17767579