Metabolic environment in substantia nigra reticulata is critical for the expression and control of hypoglycemia-induced seizures.
Seizures represent a common and serious complication of hypoglycemia. Here we studied mechanisms of control of hypoglycemic seizures induced by insulin injection in fasted and nonfasted rats. We demonstrate that fasting predisposes rats to more rapid and consistent development of hypoglycemic seizures. However, the fasting-induced decrease in baseline blood glucose concentration cannot account for the earlier onset of seizures in fasted versus nonfasted rats. Data obtained with c-Fos immunohistochemistry and [14C]2-deoxyglucose uptake implicate a prominent involvement of the substantia nigra reticulata (SNR) among other structures in the hypoglycemic seizure control. This is supported by data showing that fasting decreases the SNR expression of K(ATP) channels, which link metabolism with activity, and is further confirmed with microinfusions of K(ATP) channel agonist and antagonist. Data obtained with whole-cell and perforated patch recordings from SNR neurons in slices in vitro demonstrate that both presynaptic and postsynaptic K(ATP) channels participate in the failure of the SNR to control hypoglycemic seizures. The results suggest that fasting and insulin-induced hypoglycemia can lead to impairment in the function of the SNR, leading thus to hypoglycemic seizures.
Velísek
Libor
L
The Saul R. Korey Department of Neurology, Albert Einstein College of Medicine, Bronx, New York 10461, USA. velisek@aecom.yu.edu
Velísková
Jana
J
Chudomel
Ondrej
O
Poon
Ka-Lai
KL
Robeson
Kimberly
K
Marshall
Barbara
B
Sharma
Archana
A
Moshé
Solomon L
SL
D000818:Animals; D003847:Deoxyglucose; D004734:Energy Metabolism / Q000502:physiology*; D005508:Food Deprivation / Q000502:physiology; D007003:Hypoglycemia / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology; D054086:KATP Channels / Q000378:metabolism; D008297:Male; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D024661:Potassium Channels, Inwardly Rectifying / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000209:etiology* / Q000378:metabolism* / Q000503:physiopathology; D013378:Substantia Nigra / Q000378:metabolism* / Q000503:physiopathology; D000099161:Kcnj11 Channel
D003847:Deoxyglucose; D007328:Insulin; D054086:KATP Channels; D024661:Potassium Channels, Inwardly Rectifying; D016760:Proto-Oncogene Proteins c-fos; D000099161:Kcnj11 Channel
Neurobiol Dis. 2007 Jun;26(3):646-60
17459717
Pancreas. 2005 Aug;31(2):142-7
16025001
Brain Res. 1985 May 20;334(2):227-33
3995318
Brain Res. 1989 Jan 16;477(1-2):391-5
2539235
Exp Neurol. 1986 Jul;93(1):180-7
3732457
Science. 1987 Jul 10;237(4811):192-7
3037702
N Engl J Med. 2004 Apr 29;350(18):1838-49
15115830
Pediatr Res. 1993 Nov;34(5):634-41
8284102
Endocrinology. 2005 Dec;146(12):5514-21
16123162
Diabetes Care. 1995 Mar;18(3):361-76
7555480
Brain Res. 1987 Dec 15;465(1-2):43-58
3440212
Neuroscience. 1994 Jul;61(2):285-92
7969909
QJM. 1998 Jul;91(7):505-10
9797934
Neurobiol Dis. 2005 Dec;20(3):752-9
15950481
Brain Res. 1989 May 1;486(1):159-64
2497930
Endocrinol Metab Clin North Am. 2000 Dec;29(4):725-43
11149159
Neurosci Lett. 2004 Jan 30;355(3):173-6
14732459
Science. 2001 May 25;292(5521):1543-6
11375491
Exp Neurol. 1997 Feb;143(2):255-68
9056388
J Neurosci. 1984 Jan;4(1):251-64
6693941
Neuroscience. 1997 Sep;80(2):545-57
9284356
Exp Brain Res. 1982;47(1):105-13
6288427
Prog Biophys Mol Biol. 2003 Feb;81(2):133-76
12565699
Brain Res Bull. 1988 Nov;21(5):741-7
2851374
Pharmacology. 1988;36(1):1-8
3340650
Epilepsy Res. 1999 Dec;37(3):191-201
10584969
Brain Res. 1990 Jun 11;519(1-2):29-43
2118822
J Physiol. 2004 Jan 15;554(Pt 2):353-70
14578474
J Biol Rhythms. 2000 Oct;15(5):365-79
11039915
Brain Res. 1990 Aug 27;526(1):147-52
2127731
Neuroscience. 2002;115(3):685-96
12435407
Prog Neurobiol. 1994 Jan;42(1):33-52
7480786
Brain Res. 1989 Feb 20;480(1-2):378-82
2540881
J Neurochem. 1977 May;28(5):897-916
864466
J Clin Invest. 1995 May;95(5):2403-8
7738204
Proc Natl Acad Sci U S A. 2002 Oct 1;99(20):13278-83
12271142
Int J Obes Relat Metab Disord. 2001 Dec;25 Suppl 5:S68-72
11840219
Epilepsy Res. 1998 Sep;32(1-2):213-23
9761322
Am J Physiol Endocrinol Metab. 2007 Jun;292(6):E1801-7
17311891
Exp Neurol. 2000 Feb;161(2):481-9
10686070
J Mol Cell Cardiol. 2005 Jun;38(6):945-9
15910879
Synapse. 1996 Oct;24(2):125-34
8890454
Brain Res. 1989 Sep 25;498(1):64-72
2551457
Ann Neurol. 1985 May;17(5):421-30
4004166
J Comp Neurol. 1991 Dec 8;314(2):278-89
1787178
J Neurosci Methods. 1980 Dec;3(2):129-49
6110810
J Neurosci. 2002 Jan 1;22(1):305-14
11756514
Neurobiol Dis. 2005 Mar;18(2):346-55
15686963
Neuroscience. 1985 Feb;14(2):375-403
2859548
Eur J Neurosci. 2002 Jan;15(2):329-44
11849299
Proc Natl Acad Sci U S A. 2001 Mar 13;98(6):3549-54
11248115
Neuron. 2003 May 8;38(3):417-32
12741989
Brain Res. 1998 Dec 14;814(1-2):41-54
9838037
Neuroscience. 1996 Nov;75(1):5-12
8923517
Neuroscience. 1992;46(2):379-90
1542413
Epilepsia. 1984 Oct;25(5):574-7
6434295
Ann Neurol. 2001 Nov;50(5):596-601
11706965
Synapse. 1992 Dec;12(4):322-32
1334580
Mol Cell Biochem. 1981 Sep 25;39:305-29
6273710
Neuroscience. 1998 Apr;83(4):1155-60
9502254
Neuroscience. 2001;105(1):203-11
11483312
J Neurophysiol. 2004 Apr;91(4):1734-47
14645380
Ann Neurol. 1978 Jul;4(1):73-9
697328
Epilepsy Res. 1990 Apr;5(3):192-8
2384075
Epilepsia. 2007;48 Suppl 5:106-8
17910588
J Cereb Blood Flow Metab. 1990 Jul;10(4):499-509
2347881
Ann Neurol. 1991 Jan;29(1):72-7
1899987
Diabetes Care. 2005 Jun;28(6):1333-8
15920048
Brain Res. 2005 Feb 1;1033(1):20-7
15680335
Electroencephalogr Clin Neurophysiol. 1972 Mar;32(3):281-94
4110397
J Inherit Metab Dis. 2005;28(2):109-21
15877199
Mol Membr Biol. 2001 Apr-Jun;18(2):117-27
11463204
EMBO J. 1999 Feb 15;18(4):833-46
10022826
Ann Neurol. 2007 Feb;61(2):109-19
17315208
Epilepsy Curr. 2006 May-Jun;6(3):83-7
16761069
Brain Res Dev Brain Res. 1992 Oct 23;69(2):243-59
1424100
Brain Res. 1989 Feb 20;480(1-2):383-7
2713664
Diabetes Care. 1997 Jan;20(1):22-5
9028688
Biochem Soc Trans. 2007 Nov;35(Pt 5):1055-9
17956278
Int J Biochem Cell Biol. 2004 May;36(5):753-8
15061128
J Neurosci. 1998 Oct 15;18(20):8515-33
9763494
Neuroscience. 1990;39(2):339-49
2128373
J Neurosci. 2007 May 30;27(22):6054-63
17537977
Neurology. 2000 Jan 25;54(2):282-3
10668683
J Neurochem. 1987 Jul;49(1):121-7
3295120
Neurosci Lett. 2001 Dec;316(2):108-10
11742727
Expert Rev Mol Med. 2007 Aug 01;9(21):1-17
17666135
Proc Natl Acad Sci U S A. 2007 Jul 31;104(31):12861-6
17646659
Neuroscience. 1986 May;18(1):61-77
3016600
J Neurosci Methods. 1995 Mar;57(1):27-35
7540702
Eur J Endocrinol. 1998 Mar;138(3):240-8
9539293
J Neurosci. 2007 Apr 4;27(14):3618-25
17409226
Pharmacol Biochem Behav. 1988 Sep;31(1):153-62
2978064
J Biol Chem. 1999 Jun 25;274(26):18261-70
10373428
Brain Res. 2007 Aug 8;1162:1-8
17618607
J Anat. 2000 May;196 ( Pt 4):527-42
10923985
Eur J Neurosci. 2006 Mar;23(6):1512-22
16553614