PMID- 24605339 OWN - NLM STAT- MEDLINE DCOM- 20141015 LR - 20211021 IS - 2314-6141 (Electronic) IS - 2314-6133 (Print) VI - 2014 DP - 2014 TI - Modulation of c-Fos and BDNF protein expression in pentylenetetrazole-kindled mice following the treatment with novel antiepileptic compound HHL-6. PG - 876712 LID - 10.1155/2014/876712 [doi] LID - 876712 AB - Brain-derived neurotrophic factor (BDNF) and c-Fos are shown to promote epileptogenesis and are taken as a marker of neuronal activity. The present study investigated the expression of BDNF and c-Fos in mice brain with pentylenetetrazol- (PTZ-) induced generalized seizure and evaluated the effect of novel tryptamine derivative HHL-6 on the expression of these two markers. The subconvulsive dose of PTZ (50 mg/kg) was administered on alternate days in the experimental groups until the seizure scores 4-5 developed in the PTZ-control group. At the end of each experiment, animals were sacrificed, brain samples were collected and cryosectioned, and immunohistochemical analysis of BDNF and c-Fos protein was performed. Data obtained from two sections per mouse (n = 12 animals/group) is presented as means +/- S.E.M. The test compound HHL-6 demonstrated a potent anticonvulsant activity in the PTZ-induced seizure in mice. Significant reduction in the BDNF (P < 0.003) and c-Fos (P < 0.01) protein expression was observed in the HHL-6 treated group. Based on these results we suggest that one of the possible mechanisms of HHL-6 to inhibit epileptogenesis might be due to its controlling effect on the cellular and molecular expression of the factors that contribute to the development of epileptogenic plasticity in the CNS. FAU - Malhi, Saima Mahmood AU - Malhi SM AD - H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan. FAU - Jawed, Huma AU - Jawed H AUID- ORCID: 0000-0003-3643-4225 AD - H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan. FAU - Hanif, Farina AU - Hanif F AD - Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan. FAU - Ashraf, Nadeem AU - Ashraf N AD - H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan. FAU - Zubair, Farhat AU - Zubair F AD - H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan. FAU - Siddiqui, Bina S AU - Siddiqui BS AD - H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan. FAU - Begum, Sabira AU - Begum S AD - H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan. FAU - Kabir, Nurul AU - Kabir N AD - Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan. FAU - Simjee, Shabana Usman AU - Simjee SU AD - H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan ; Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan. LA - eng PT - Journal Article DEP - 20140129 PL - United States TA - Biomed Res Int JT - BioMed research international JID - 101600173 RN - 0 (Anticonvulsants) RN - 0 (Brain-Derived Neurotrophic Factor) RN - WM5Z385K7T (Pentylenetetrazole) SB - IM MH - Animals MH - Anticonvulsants/administration & dosage MH - Brain/drug effects/metabolism/pathology MH - Brain-Derived Neurotrophic Factor/*biosynthesis/genetics MH - Disease Models, Animal MH - Epilepsy/*drug therapy/genetics MH - Gene Expression Regulation/drug effects MH - Genes, fos/*genetics MH - Mice MH - Pentylenetetrazole/*administration & dosage MH - Seizures/*drug therapy/pathology PMC - PMC3925558 EDAT- 2014/03/08 06:00 MHDA- 2014/10/16 06:00 PMCR- 2014/01/29 CRDT- 2014/03/08 06:00 PHST- 2013/04/15 00:00 [received] PHST- 2013/10/22 00:00 [revised] PHST- 2013/10/30 00:00 [accepted] PHST- 2014/03/08 06:00 [entrez] PHST- 2014/03/08 06:00 [pubmed] PHST- 2014/10/16 06:00 [medline] PHST- 2014/01/29 00:00 [pmc-release] AID - 10.1155/2014/876712 [doi] PST - ppublish SO - Biomed Res Int. 2014;2014:876712. doi: 10.1155/2014/876712. Epub 2014 Jan 29.