title: Carbamazepine protects against megencephaly and abnormal expression of BDNF and Nogo signaling components in the mceph/mceph mouse.
abstract: Carbamazepine (CBZ) is a commonly used antiepileptic drug known to block voltage-gated sodium channels. Infants exposed to CBZ in utero show reduced head circumference, for reasons unknown. We investigated CBZ's effect on neural growth in megencephaly (mceph/mceph) mice lacking functional Kv1.1. Mice fed with CBZ were assessed for brain structure size, seizure behavior and expression of markers for neuronal plasticity and rescue in brain. CBZ counteracted brain overgrowth and the increased size of neurons in the mceph/mceph mouse. These effects of CBZ occurred at doses that did not fully suppress epileptic behavior. Furthermore, CBZ normalized Bdnf mRNA levels and mRNA species encoding Nogo signaling pathway proteins. In conclusion, CBZ protects efficiently against abnormal growth and abnormal expression patterns of nerve growth signaling systems in the mceph/mceph brain. These observations and the effect of CBZ in utero suggest that CBZ treatment might be advantageous in some types of human idiopathic megalencephaly.
authors.affiliation: Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska Hospital L8:00, 171 76 Stockholm, Sweden. catharina.lavebratt@ki.se
authors.forename: Catharina
authors.initials: C
authors.lastname: Lavebratt
authors.forename: Alexandra
authors.initials: A
authors.lastname: Trifunovski
authors.forename: Ann-Sophie
authors.initials: AS
authors.lastname: Persson
authors.forename: Fu-Hua
authors.initials: FH
authors.lastname: Wang
authors.forename: Tomas
authors.initials: T
authors.lastname: Klason
authors.forename: Inger
authors.initials: I
authors.lastname: Ohman
authors.forename: Anna
authors.initials: A
authors.lastname: Josephsson
authors.forename: Lars
authors.initials: L
authors.lastname: Olson
authors.forename: Christian
authors.initials: C
authors.lastname: Spenger
authors.forename: Martin
authors.initials: M
authors.lastname: Schalling
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology / Q000627:therapeutic use; D001921:Brain / Q000002:abnormalities / Q000187:drug effects* / Q000503:physiopathology; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D002220:Carbamazepine / Q000494:pharmacology* / Q000627:therapeutic use; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D049108:Cell Enlargement / Q000187:drug effects; D004195:Disease Models, Animal; D004827:Epilepsy / Q000188:drug therapy / Q000503:physiopathology / Q000517:prevention & control; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000502:physiology; D006131:Growth Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D051379:Mice; D008807:Mice, Inbred BALB C; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D009185:Myelin Proteins / Q000235:genetics / Q000378:metabolism*; D009421:Nervous System Malformations / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*; D000070798:Nogo Proteins; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D016896:Treatment Outcome
chemical_list: D000927:Anticonvulsants; D019208:Brain-Derived Neurotrophic Factor; D006131:Growth Inhibitors; D009185:Myelin Proteins; D000070798:Nogo Proteins; D012333:RNA, Messenger; C000603199:RTN4 protein, human; C000603201:Rtn4 protein, mouse; D002220:Carbamazepine