Carbamazepine protects against megencephaly and abnormal expression of BDNF and Nogo signaling components in the mceph/mceph mouse

• Published in: Neurobiology of disease Vol. 24; no. 2; pp. 374 - 383
• Main Authors: Lavebratt, Catharina, Trifunovski, Alexandra, Persson, Ann-Sophie, Wang, Fu-Hua, Klason, Tomas, Öhman, Inger, Josephsson, Anna, Olson, Lars, Spenger, Christian, Schalling, Martin
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.11.2006; Elsevier
• Subjects: Animals; Anticonvulsants - pharmacology; Anticonvulsants - therapeutic use; Antiepileptic drug, potassium channel; Brain - abnormalities; Brain - drug effects; Brain - physiopathology; Brain-Derived Neurotrophic Factor - genetics; Brain-Derived Neurotrophic Factor - metabolism; Carbamazepine - pharmacology; Carbamazepine - therapeutic use; Cell Differentiation - drug effects; Cell Differentiation - physiology; Cell Enlargement - drug effects; Disease Models, Animal; Epilepsy; Epilepsy - drug therapy; Epilepsy - physiopathology; Epilepsy - prevention & control; Gene Expression Regulation, Developmental - drug effects; Gene Expression Regulation, Developmental - physiology; Growth Inhibitors - pharmacology; Growth Inhibitors - therapeutic use; Medicin och hälsovetenskap; Megalencephaly; Mice; Mice, Inbred BALB C; Mice, Mutant Strains; Mice, Transgenic; Myelin Proteins - genetics; Myelin Proteins - metabolism; Nervous System Malformations - genetics; Nervous System Malformations - metabolism; Nervous System Malformations - prevention & control; Nogo Proteins; RNA, Messenger - drug effects; RNA, Messenger - metabolism; Signal Transduction - drug effects; Signal Transduction - physiology; Treatment Outcome; Epilepsy; Megalencephaly; Antiepileptic drug, potassium channel
• ISSN: 0969-9961; 1095-953X
• DOI: 10.1016/j.nbd.2006.07.018

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.