title: The expression of kainate receptor subunits in hippocampal astrocytes after experimentally induced status epilepticus.
abstract: Astrocytes have emerged as active participants of synaptic transmission and are increasingly implicated in neurologic disorders including epilepsy. Adult glial fibrillary acidic protein (GFAP)-positive hippocampal astrocytes are not known for ionotropic glutamate receptor expression under basal conditions. Using a chemoconvulsive status epilepticus (SE) model of temporal lobe epilepsy, we show by immunohistochemistry and colocalization analysis that reactive hippocampal astrocytes express kainate receptor (KAR) subunits after SE. In the CA1 region, GluK1, GluK2/3, GluK4, and GluK5 subunit expression was observed in GFAP-positive astrocytes during the seizure-free or "latent" period 1 week after SE. At 8 weeks after SE, a time after SE when spontaneous behavioral seizures occur, the GluK1 and GluK5 subunits remained expressed at significant levels. Kainate receptor subunit expression was found in astrocytes in the hippocampus and surrounding cortex but not in GFAP-positive astrocytes of striatum, olfactory bulb, or brainstem. To examine hippocampal KAR expression more broadly, astroglial-enriched tissue fractions were prepared from dissected hippocampi and were found to have greater GluK4 expression after SE than controls. These results demonstrate that astrocytes begin to express KARs after seizure activity and suggest that their expression may contribute to the pathophysiology of epilepsy.
authors.affiliation: From the Department of Pharmacology and Toxicology (JRV, KSW), Interdepartmental Program in Neuroscience (DKT, KSW), and Department of Bioengineering (KET), University of Utah, Salt Lake City, Utah.
authors.forename: Jay R
authors.initials: JR
authors.lastname: Vargas
authors.forename: D Koji
authors.initials: DK
authors.lastname: Takahashi
authors.forename: Kyle E
authors.initials: KE
authors.lastname: Thomson
authors.forename: Karen S
authors.initials: KS
authors.lastname: Wilcox
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005911:Gliosis / Q000235:genetics / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism*; D007608:Kainic Acid; D008297:Male; D009474:Neurons / Q000378:metabolism; D010862:Pilocarpine; D021122:Protein Subunits / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018092:Kainic Acid Receptors / Q000378:metabolism*; D012640:Seizures / Q000378:metabolism; D013226:Status Epilepticus / Q000139:chemically induced / Q000378:metabolism*
chemical_list: D005904:Glial Fibrillary Acidic Protein; D007608:Kainic Acid; D010862:Pilocarpine; D021122:Protein Subunits; D018092:Kainic Acid Receptors
references.citation: J Neurochem. 2006 Feb;96(3):656-68
references.pmid: 16405496
references.citation: Trends Neurosci. 2000 Nov;23(11):580-7
references.pmid: 11074268
references.citation: Glia. 2006 Oct;54(5):358-68
references.pmid: 16886201
references.citation: Brain Res Mol Brain Res. 2000 Sep 30;81(1-2):164-76
references.pmid: 11000488
references.citation: J Histochem Cytochem. 1977 Jul;25(7):741-53
references.pmid: 70454
references.citation: Epilepsy Res. 2007 May;74(2-3):97-106
references.pmid: 17395429
references.citation: Brain Res Rev. 2010 May;63(1-2):130-7
references.pmid: 20018210
references.citation: J Neurochem. 1993 Mar;60(3):877-85
references.pmid: 8094745
references.citation: Neurobiol Dis. 2010 Dec;40(3):573-85
references.pmid: 20691786
references.citation: Pflugers Arch. 1994 Feb;426(3-4):310-9
references.pmid: 8183642
references.citation: J Neurosci. 2008 May 7;28(19):4967-73
references.pmid: 18463250
references.citation: Neurotherapeutics. 2010 Oct;7(4):424-38
references.pmid: 20880506
references.citation: Glia. 1995 Oct;15(2):195-202
references.pmid: 8567071
references.citation: J Neurosci. 1985 Apr;5(4):1016-22
references.pmid: 3981241
references.citation: Brain Res Rev. 2010 May;63(1-2):212-21
references.pmid: 19883685
references.citation: Epilepsy Res Suppl. 1996;12:9-20
references.pmid: 9302499
references.citation: J Neurosci. 2009 Feb 18;29(7):2103-12
references.pmid: 19228963
references.citation: Nature. 2006 Apr 20;440(7087):1054-9
references.pmid: 16547515
references.citation: J Cereb Blood Flow Metab. 1997 Mar;17(3):290-300
references.pmid: 9119902
references.citation: Dialogues Clin Neurosci. 2008;10(1):39-45
references.pmid: 18472483
references.citation: Nat Med. 2005 Sep;11(9):973-81
references.pmid: 16116433
references.citation: J Neurosci Res. 2003 Aug 1;73(3):416-26
references.pmid: 12868075
references.citation: Neuron. 2004 Sep 2;43(5):729-43
references.pmid: 15339653
references.citation: Glia. 2006 Nov 15;54(7):700-715
references.pmid: 17006898
references.citation: Science. 1990 Jan 26;247(4941):470-3
references.pmid: 1967852
references.citation: Hippocampus. 1994 Feb;4(1):19-35
references.pmid: 7914797
references.citation: Neurochem Res. 1994 Sep;19(9):1145-50
references.pmid: 7824067
references.citation: Glia. 1997 Nov;21(3):332-7
references.pmid: 9383042
references.citation: J Neurosci. 2008 Jan 2;28(1):264-78
references.pmid: 18171944
references.citation: Glia. 1993 Sep;9(1):48-56
references.pmid: 7902337
references.citation: Neuron. 2003 Jul 31;39(3):543-53
references.pmid: 12895426
references.citation: J Neurosci. 2003 Sep 3;23(22):8013-9
references.pmid: 12954862
references.citation: J Neurosci. 2003 Apr 15;23(8):3364-72
references.pmid: 12716944
references.citation: J Neurosci. 2008 Mar 26;28(13):3264-76
references.pmid: 18367594
references.citation: Pharmacol Rev. 2010 Sep;62(3):405-96
references.pmid: 20716669
references.citation: Brain Res Mol Brain Res. 2005 May 20;136(1-2):38-44
references.pmid: 15893585
references.citation: Eur J Pharmacol. 2002 Aug 2;449(1-2):71-4
references.pmid: 12163108
references.citation: J Neurosci. 1996 Aug 15;16(16):5073-81
references.pmid: 8756437
references.citation: Physiol Rev. 2001 Jul;81(3):971-98
references.pmid: 11427689
references.citation: Proc Natl Acad Sci U S A. 1994 Oct 25;91(22):10625-9
references.pmid: 7938003
references.citation: J Neurosci. 2006 Sep 6;26(36):9312-22
references.pmid: 16957087
references.citation: Brain Res Dev Brain Res. 2002 Dec 15;139(2):227-36
references.pmid: 12480137
references.citation: Proc Natl Acad Sci U S A. 2003 Oct 14;100(21):12456-61
references.pmid: 14530410
references.citation: Electroencephalogr Clin Neurophysiol. 1972 Mar;32(3):281-94
references.pmid: 4110397
references.citation: Science. 2002 Mar 22;295(5563):2282-5
references.pmid: 11910117
references.citation: Proc Natl Acad Sci U S A. 2004 Oct 12;101(41):14937-42
references.pmid: 15466714
references.citation: Glia. 2006 Nov 15;54(7):716-725
references.pmid: 17006900
references.citation: J Neurosci. 1994 Sep;14(9):5525-47
references.pmid: 8083752
references.citation: Nat Protoc. 2008;3(11):1718-28
references.pmid: 18927557
references.citation: Glia. 1995 Feb;13(2):101-12
references.pmid: 7544323
references.citation: Nature. 1994 Jun 30;369(6483):744-7
references.pmid: 7911978
references.citation: Epilepsy Res. 1998 Jun;31(1):73-84
references.pmid: 9696302
references.citation: Nature. 1998 Jan 15;391(6664):281-5
references.pmid: 9440691
references.citation: Neuroscience. 2012 Sep 18;220:237-46
references.pmid: 22698689
references.citation: Glia. 1993 Aug;8(4):277-91
references.pmid: 8406684
references.citation: Epilepsia. 2012 Jan;53(1):134-46
references.pmid: 22150444
references.citation: Trends Neurosci. 2007 Dec;30(12):630-7
references.pmid: 17981346
references.citation: Eur J Neurol. 2006 Mar;13(3):277-82
references.pmid: 16618346
references.citation: Epilepsia. 1999 Jun;40(6):708-12
references.pmid: 10368067