title: Behavioral deficit and decreased GABA receptor functional regulation in the hippocampus of epileptic rats: effect of Bacopa monnieri.
abstract: In the present study, alterations of the General GABA and GABA(A) receptors in the hippocampus of pilocarpine-induced temporal lobe epileptic rats and the therapeutic application of Bacopa monnieri and its active component Bacoside-A were investigated. Bacopa monnieri (Linn.) is a herbaceous plant belonging to the family Scrophulariaceae. Hippocampus is the major region of the brain belonging to the limbic system and plays an important role in epileptogenesis, memory and learning. Scatchard analysis of [³H]GABA and [³H]bicuculline in the hippocampus of the epileptic rat showed significant decrease in B(max) (P < 0.001) compared to control. Real Time PCR amplification of GABA(A) receptor sub-units such as GABA(Aά₁), GABA(Aά₅) GABA(Aδ), and GAD were down regulated (P < 0.001) in the hippocampus of the epileptic rats compared to control. GABA(Aγ) subunit was up regulated. Epileptic rats have deficit in the radial arm and Y maze performance. Bacopa monnieri and Bacoside-A treatment reverses all these changes near to control. Our results suggest that decreased GABA receptors in the hippocampus have an important role in epilepsy associated behavioral deficit, Bacopa monnieri and Bacoside-A have clinical significance in the management of epilepsy.
authors.affiliation: Molecular Neurobiology and Cell Biology Unit, Centre for Neuroscience, Department of Biotechnology, Cochin University of Science and Technology, Cochin, 682022 Kerala, India.
authors.forename: Jobin
authors.initials: J
authors.lastname: Mathew
authors.forename: Gireesh
authors.initials: G
authors.lastname: Gangadharan
authors.forename: Korah P
authors.initials: KP
authors.lastname: Kuruvilla
authors.forename: C S
authors.initials: CS
authors.lastname: Paulose
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D034681:Bacopa / Q000737:chemistry* / Q000378:metabolism; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology*; D002220:Carbamazepine / Q000494:pharmacology; D004827:Epilepsy / Q000188:drug therapy* / Q000503:physiopathology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009483:Neuropsychological Tests; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D018079:Receptors, GABA / Q000378:metabolism*; D012503:Saponins / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D014315:Triterpenes / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000927:Anticonvulsants; D010936:Plant Extracts; D018079:Receptors, GABA; D012503:Saponins; D014315:Triterpenes; C500175:bacoside A; D002220:Carbamazepine
references.citation: Neuropsychologia. 1979;17(6):669-82
references.pmid: 522981
references.citation: Proc Natl Acad Sci U S A. 2003 Apr 1;100(7):4293-8
references.pmid: 12634427
references.citation: Exp Neurol. 2007 Jun;205(2):501-5
references.pmid: 17442304
references.citation: Brain. 2000 Mar;123 Pt 3:472-83
references.pmid: 10686171
references.citation: Behav Brain Sci. 1999 Jun;22(3):425-44; discussion 444-89
references.pmid: 11301518
references.citation: Indian J Physiol Pharmacol. 1967 Jan;11(1):33-43
references.pmid: 5630157
references.citation: Indian J Exp Biol. 1966 Oct;4(4):216-9
references.pmid: 5977555
references.citation: Lancet. 2001 Jan 20;357(9251):216-22
references.pmid: 11213111
references.citation: J Cogn Neurosci. 1994 Fall;6(4):305-20
references.pmid: 23961727
references.citation: Phytomedicine. 1998 Apr;5(2):77-82
references.pmid: 23195757
references.citation: Phytomedicine. 2002 Apr;9(3):207-11
references.pmid: 12046860
references.citation: Learn Mem. 2004 Nov-Dec;11(6):794-6
references.pmid: 15537736
references.citation: Brain. 2000 Apr;123 ( Pt 4):800-15
references.pmid: 10734011
references.citation: J Neurol Neurosurg Psychiatry. 2005 Aug;76(8):1080-3
references.pmid: 16024883
references.citation: Phytomedicine. 2005 Apr;12(4):305-17
references.pmid: 15898709
references.citation: Epilepsia. 2004 Nov;45(11):1443-7
references.pmid: 15509245
references.citation: Phytomedicine. 2004 Feb;11(2-3):264-8
references.pmid: 15070183
references.citation: Hippocampus. 2000;10(4):420-30
references.pmid: 10985281
references.citation: Hippocampus. 2004;14(6):785-96
references.pmid: 15318335
references.citation: Neurochem Res. 2008 Sep;33(9):1663-71
references.pmid: 17940877
references.citation: Neurobiol Learn Mem. 2003 Jan;79(1):32-40
references.pmid: 12482677
references.citation: Neuropsychopharmacology. 2002 Aug;27(2):279-81
references.pmid: 12093601
references.citation: J Neurosci. 2000 Dec 1;20(23):8788-801
references.pmid: 11102487
references.citation: Proc Natl Acad Sci U S A. 1994 Apr 12;91(8):3058-62
references.pmid: 8159706
references.citation: Neurology. 2003 Mar 25;60(6):951-9
references.pmid: 12654959
references.citation: Proc Natl Acad Sci U S A. 2001 Nov 20;98(24):14033-7
references.pmid: 11717462
references.citation: Life Sci. 2003 Aug 8;73(12):1517-26
references.pmid: 12865091
references.citation: Nat Genet. 2001 May;28(1):49-52
references.pmid: 11326275
references.citation: N Engl J Med. 2003 Sep 25;349(13):1257-66
references.pmid: 14507951
references.citation: Nat Genet. 2001 May;28(1):46-8
references.pmid: 11326274
references.citation: J Neurosci. 1999 Oct 1;19(19):8637-45
references.pmid: 10493764
references.citation: J Neurochem. 1981 Aug;37(2):418-21
references.pmid: 6267202
references.citation: Neuroscience. 2007 Jul 29;147(4):1059-65
references.pmid: 17601672
references.citation: Phytomedicine. 2001 Nov;8(6):472-6
references.pmid: 11824524
references.citation: J Neurosci. 2000 Jul 15;20(14):5401-19
references.pmid: 10884325
references.citation: J Ethnopharmacol. 2008 Oct 30;120(1):112-7
references.pmid: 18755259
references.citation: Electroencephalogr Clin Neurophysiol. 1972 Mar;32(3):269-79
references.pmid: 4110396
references.citation: Phytother Res. 2002 Nov;16(7):639-45
references.pmid: 12410544
references.citation: Neuron. 2000 Apr;26(1):197-205
references.pmid: 10798404
references.citation: Psychopharmacology (Berl). 2001 Aug;156(4):481-4
references.pmid: 11498727
references.citation: Nat Genet. 2002 Jun;31(2):184-9
references.pmid: 11992121
references.citation: Nat Med. 1998 Oct;4(10):1166-72
references.pmid: 9771750
references.citation: Brain. 2008 Sep;131(Pt 9):2243-63
references.pmid: 18669495
references.citation: Cancer Res. 2002 Nov 15;62(22):6467-9
references.pmid: 12438237
references.citation: Brain Res. 1997 Jun 6;759(1):76-83
references.pmid: 9219865
references.citation: Behav Brain Res. 1990 Nov 15;40(2):119-29
references.pmid: 2285473
references.citation: J Neurophysiol. 1999 Mar;81(3):1296-307
references.pmid: 10085356
references.citation: Acta Pharmacol Sin. 2005 Nov;26(11):1297-302
references.pmid: 16225750
references.citation: J Ethnopharmacol. 1982 Mar;5(2):205-14
references.pmid: 7057659
references.citation: Phytother Res. 2000 May;14(3):174-9
references.pmid: 10815010
references.citation: Neuroscience. 1997 Oct;80(4):1019-32
references.pmid: 9284057
references.citation: Brain Res. 1979 May 11;167(2):323-36
references.pmid: 445132
references.citation: Neuroreport. 2003 Oct 27;14(15):1979-82
references.pmid: 14561933
references.citation: Phytother Res. 2003 Sep;17(8):870-5
references.pmid: 13680815
references.citation: Fitoterapia. 2010 Jul;81(5):315-22
references.pmid: 19944749
references.citation: Brain Res. 1981 Mar 23;209(1):177-88
references.pmid: 6260300
references.citation: Epilepsia. 2002 Apr;43(4):350-7
references.pmid: 11952764
references.citation: J Physiol. 2005 Jan 1;562(Pt 1):37-46
references.pmid: 15528237
references.citation: J Biol Chem. 1951 Nov;193(1):265-75
references.pmid: 14907713
references.citation: Annu Rev Neurosci. 2004;27:279-306
references.pmid: 15217334