Carbamazepine protects against neuronal hyperplasia and abnormal gene expression in the megencephaly mouse.
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 Kv1.1(mceph/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.
Almgren
Malin
M
Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska Hospital L8:00, 171 76 Stockholm, Sweden. malin.almgren@ki.se
Nyengaard
Jens R
JR
Persson
Bengt
B
Lavebratt
Catharina
C
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D001345:Autoradiography; D001483:Base Sequence; D002220:Carbamazepine / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006624:Hippocampus / Q000002:abnormalities* / Q000254:growth & development / Q000378:metabolism* / Q000473:pathology; D006965:Hyperplasia; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D051379:Mice; D008817:Mice, Mutant Strains; D009473:Neuronal Plasticity / Q000187:drug effects / Q000235:genetics; D009474:Neurons / Q000187:drug effects / Q000473:pathology*; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D012313:RNA / Q000235:genetics / Q000378:metabolism
D000927:Anticonvulsants; D002220:Carbamazepine; D012313:RNA