Effects of antiepileptic drugs on mRNA levels of BDNF and NT-3 and cell neogenesis in the developing rat brain.
Epilepsy is a common neurological disorder that occurs more frequently in childhood than in adulthood. Antiepileptic drugs (AEDs) which are used to treat seizures in pregnant women, infants, and young children may cause cognitive impairment or other uncertain injury. However, the exact mechanisms responsible for adverse effects of AEDs in the developing brain are still not clear. In the present study, we investigate the effects of AEDs on mRNA levels of brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3), cell neogenesis and mossy fiber sprouting (MFS) in the developing rat brain. Long-term treatment with Phenobarbital (40mg/kg), valproate (100mg/kg) and topiramate (40mg/kg) reduces BDNF and NT-3 mRNA expression in the developing brain, while lamotrigine reduces mRNA expression only at high dose level (80mg/kg). Cell neogenesis only increases in the rats treated with valproate and lamotrigine. And no differences are observed between the control group and the AEDs-treated groups in the Timm scores of the CA3 region and supragranular region. Our findings present some possible mechanisms to explain why different AEDs cause different cognitive impairment.
Shi
Xiu-Yu
XY
Department of Pediatrics, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, PR China.
Wang
Ji-Wen
JW
Cui
Hong
H
Li
Bao-Min
BM
Lei
Ge-Fei
GF
Sun
Ruo-Peng
RP
D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D000927:Anticonvulsants / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000254:growth & development / Q000473:pathology; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics* / Q000378:metabolism; D001973:Bromodeoxyuridine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects; D019599:Mossy Fibers, Hippocampal / Q000187:drug effects / Q000378:metabolism; D055495:Neurogenesis / Q000187:drug effects*; D020933:Neurotrophin 3 / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D000927:Anticonvulsants; D019208:Brain-Derived Neurotrophic Factor; D020933:Neurotrophin 3; D012333:RNA, Messenger; D001973:Bromodeoxyuridine