Carbamazepine treatment recovered low N-acetylaspartate+N-acetylaspartylglutamate (tNAA) levels in the megencephaly mouse BALB/cByJ-Kv1.1(mceph/mceph).
Megencephaly mice (BALB/cByJ-Kv1.1(mceph/mceph)) display excessive brain growth and seizures related to a mutation within the potassium channel gene Kv1.1 producing a malfunctioning protein. (1)H Magnetic resonance spectroscopy (MRS) provides means to study brain transmitters and metabolites in vivo. We applied MRS to pinpoint differences in hippocampus between mceph/mceph and wild type (wt) mice. Carbamazepine (CBZ) protects against brain overgrowth in mceph/mceph. Therefore, the effects of durable oral CBZ treatment on the MR spectra were investigated. LCModel was used for spectra quantification and multivariate data analysis applied to detect group differences. mceph/mceph mice had lower levels of N-acetylaspartate+N-acetylaspartylglutamate (tNAA) and choline-containing (tCho) compounds compared to wt mice. Glutamate, glutamine, taurine and myo-inositol levels were similar in wt and mceph/mceph. Furthermore, CBZ treatment recovered tCho and tNAA levels in mceph/mceph. Thus, distinct differences in MRS spectra between mceph/mceph and wt mice were depicted and treatment effects of CBZ were monitored using MRS.
Westman
Eric
E
Department of Neurobiology, Health Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.
Spenger
Christian
C
Wahlund
Lars-Olof
LO
Lavebratt
Catharina
C
D000596:Amino Acids / Q000378:metabolism; D000758:Anesthesia; D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D001921:Brain / Q000002:abnormalities* / Q000473:pathology; D002220:Carbamazepine / Q000494:pharmacology*; D002794:Choline / Q000378:metabolism; D003627:Data Interpretation, Statistical; D004151:Dipeptides / Q000378:metabolism*; D005260:Female; D051662:Kv1.1 Potassium Channel / Q000235:genetics*; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D012727:Sex Characteristics
D000596:Amino Acids; D004151:Dipeptides; D051662:Kv1.1 Potassium Channel; C027172:isospaglumic acid; D001224:Aspartic Acid; D002220:Carbamazepine; C000179:N-acetylaspartate; D002794:Choline