Carbamazepine protects against neuronal hyperplasia and abnormal gene expression in the megencephaly mouse

Neurobiology of Disease

Jens R. Nyengaard¹  Catharina Lavebratt²  Malin Almgren³  Bengt Persson⁴ 

[1] Corresponding author. Fax: [phone].;Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden;Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska Hospital L8:00, 171 76 Stockholm, Sweden;Stereology and Electron Microscopy Research Laboratory and MIND Center, Aarhus University, Aarhus, Denmark;

关键词: Epilepsy;    Antiepileptic drugs;    Carbamzepine;    Neurogenesis;    Apoptosis;    Megalencephaly;   

DOI  :  

来源: DOAJ

【 摘 要 】

Carbamazepine (CBZ) is an anticonvulsant drug used to treat epilepsy and mood disorders. However, it can cause birth defects like reduced head circumference. It was recently shown to protect against brain overgrowth and seizure-induced abnormal plasticity in the megalencephalic mice Kv1.1mceph/mceph, (mceph/mceph) despite remaining seizures. The mceph/mceph mouse displays two-fold enlarged hippocampus due to more neurons and astrocytes. Using stereology, we found that CBZ normalized the number of neurons and astrocytes in mceph/mceph hippocampus. To characterize CBZ's protective ability on brain growth we studied the gene expression profile of mceph/mceph and wild type hippocampus, with and without CBZ treatment. Microarray analysis revealed transcripts involved in proliferation, differentiation and apoptosis including; NPY, Penk, Vgf, Mlc1, Sstr4, ApoD, Ndn, Aatk, Rgs2 and Gabra5, where Vgf may be of particular interest. The results also support CBZ's effect on synaptic transmission through GABA A receptors, which could promote apoptotic neurodegeneration, affecting cell number.

【 授权许可】

Unknown