title: Suppression of c-Fos protein and mRNA expression in pentylenetetrazole-induced kindled mouse brain by isoxylitones.
abstract: An early immediate gene c-fos has been proposed as the gene responsible for turning on molecular events that might underlie the long-term neural changes occurring during kindling. We have evaluated the effects of novel anticonvulsant isomeric compounds isoxylitones [(E/Z)-2-propanone-1,3,5,5-trimethyl-2-cyclohexen-1-ylidine] on the c-Fos protein and mRNA expression in the brain samples of kindled mice and compared it with the normal and untreated kindled groups. Kindling was induced in male NMRI mice by repeated administration of sub-convulsive dose (50 mg/kg) of pentylenetetrazole (PTZ) until a seizure score of 4-5 was achieved. The c-Fos expression was quantified by combination of immunohistochemistry and RT-PCR protocols. Both the immunohistochemical and RT-PCR analysis revealed a marked increase in the expression of c-fos mRNA and protein in the brain regions tested in case of PTZ-kindled control group compared to normal control. In contrast, the isoxylitone (30 mg/kg)-treated group demonstrated significant reduction of c-Fos expression compared to PTZ-kindled control animals. However, low expression of c-fos mRNA was only detected in the thalamus of the isoxylitone-treated brain samples. Based on these observations, we suggest that isoxylitones may have the capacity to control the seizure pattern by mechanism such as the suppression of c-Fos protein and mRNA levels in different regions of the brain. Further investigations to explore the mechanism of action of these compounds are under process.
authors.affiliation: H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences (ICCBS), University of Karachi, Karachi, 75270, Pakistan. shabana.simjee@iccs.edu
authors.forename: Shabana Usman
authors.initials: SU
authors.lastname: Simjee
authors.forename: Farzana
authors.initials: F
authors.lastname: Shaheen
authors.forename: M Iqbal
authors.initials: MI
authors.lastname: Choudhary
authors.forename: Atta-Ur
authors.initials: AU
authors.lastname: Rahman
authors.forename: Siddiqua
authors.initials: S
authors.lastname: Jamall
authors.forename: Syed Uzair Ali
authors.initials: SU
authors.lastname: Shah
authors.forename: Noureen
authors.initials: N
authors.lastname: Khan
authors.forename: Nurul
authors.initials: N
authors.lastname: Kabir
authors.forename: Nadeem
authors.initials: N
authors.lastname: Ashraf
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000737:chemistry / Q000494:pharmacology*; D003292:Convulsants / Q000494:pharmacology; D053138:Cyclohexenes / Q000494:pharmacology*; D007659:Ketones / Q000494:pharmacology*; D007696:Kindling, Neurologic / Q000187:drug effects* / Q000502:physiology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010433:Pentylenetetrazole / Q000494:pharmacology*; D016760:Proto-Oncogene Proteins c-fos / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*
chemical_list: C579616:1,3,5,5-trimethyl-2-cyclohexen-1-ylidine-2-propanone; D000927:Anticonvulsants; D003292:Convulsants; D053138:Cyclohexenes; D007659:Ketones; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D010433:Pentylenetetrazole