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...
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doaj-e88af1ebb0a44807abb8814b43bf08982021-03-20T04:53:18ZengElsevierNeurobiology of Disease1095-953X2006-11-01242374383Carbamazepine protects against megencephaly and abnormal expression of BDNF and Nogo signaling components in the mceph/mceph mouseCatharina Lavebratt0Alexandra Trifunovski1Ann-Sophie Persson2Fu-Hua Wang3Tomas Klason4Inger Öhman5Anna Josephsson6Lars Olson7Christian Spenger8Martin Schalling9Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska Hospital L8:00, 171 76 Stockholm, Sweden; Corresponding author. Fax: +46 8 5177 3909.Department of Neuroscience, Karolinska Institutet, Retzius Street 8, 171 77 Stockholm, SwedenDepartment of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska Hospital L8:00, 171 76 Stockholm, SwedenDepartment of Neuroscience, Karolinska Institutet, Retzius Street 8, 171 77 Stockholm, Sweden; Division of Bioscience, House 212, AstraZeneca R&D Södertälje, 151 85 Södertälje, SwedenDivision of Bioscience, House 212, AstraZeneca R&D Södertälje, 151 85 Södertälje, SwedenDepartment of Internal Medicine, Division of Clinical Pharmacology, Karolinska Institutet, Karolinska Hospital L7:04, 171 76 Stockholm, SwedenDepartment of Neuroscience, Karolinska Institutet, Retzius Street 8, 171 77 Stockholm, SwedenDepartment of Neuroscience, Karolinska Institutet, Retzius Street 8, 171 77 Stockholm, SwedenDepartment of Neuroscience, Karolinska Institutet, Retzius Street 8, 171 77 Stockholm, Sweden; Division of Bioscience, House 212, AstraZeneca R&D Södertälje, 151 85 Södertälje, SwedenDepartment of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska Hospital L8:00, 171 76 Stockholm, SwedenCarbamazepine (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.http://www.sciencedirect.com/science/article/pii/S0969996106001756MegalencephalyEpilepsyAntiepileptic drug, potassium channel |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Catharina Lavebratt Alexandra Trifunovski Ann-Sophie Persson Fu-Hua Wang Tomas Klason Inger Öhman Anna Josephsson Lars Olson Christian Spenger Martin Schalling |
spellingShingle |
Catharina Lavebratt Alexandra Trifunovski Ann-Sophie Persson Fu-Hua Wang Tomas Klason Inger Öhman Anna Josephsson Lars Olson Christian Spenger Martin Schalling Carbamazepine protects against megencephaly and abnormal expression of BDNF and Nogo signaling components in the mceph/mceph mouse Neurobiology of Disease Megalencephaly Epilepsy Antiepileptic drug, potassium channel |
author_facet |
Catharina Lavebratt Alexandra Trifunovski Ann-Sophie Persson Fu-Hua Wang Tomas Klason Inger Öhman Anna Josephsson Lars Olson Christian Spenger Martin Schalling |
author_sort |
Catharina Lavebratt |
title |
Carbamazepine protects against megencephaly and abnormal expression of BDNF and Nogo signaling components in the mceph/mceph mouse |
title_short |
Carbamazepine protects against megencephaly and abnormal expression of BDNF and Nogo signaling components in the mceph/mceph mouse |
title_full |
Carbamazepine protects against megencephaly and abnormal expression of BDNF and Nogo signaling components in the mceph/mceph mouse |
title_fullStr |
Carbamazepine protects against megencephaly and abnormal expression of BDNF and Nogo signaling components in the mceph/mceph mouse |
title_full_unstemmed |
Carbamazepine protects against megencephaly and abnormal expression of BDNF and Nogo signaling components in the mceph/mceph mouse |
title_sort |
carbamazepine protects against megencephaly and abnormal expression of bdnf and nogo signaling components in the mceph/mceph mouse |
publisher |
Elsevier |
series |
Neurobiology of Disease |
issn |
1095-953X |
publishDate |
2006-11-01 |
description |
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. |
topic |
Megalencephaly Epilepsy Antiepileptic drug, potassium channel |
url |
http://www.sciencedirect.com/science/article/pii/S0969996106001756 |
work_keys_str_mv |
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