Carbamazepine protects against megencephaly and abnormal expression of BDNF and Nogo signaling components in the mceph/mceph mouse.
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.
Lavebratt
Catharina
C
Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska Hospital L8:00, 171 76 Stockholm, Sweden. catharina.lavebratt@ki.se
Trifunovski
Alexandra
A
Persson
Ann-Sophie
AS
Wang
Fu-Hua
FH
Klason
Tomas
T
Ohman
Inger
I
Josephsson
Anna
A
Olson
Lars
L
Spenger
Christian
C
Schalling
Martin
M
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
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