Lamotrigine increases gene expression of GABA-A receptor beta3 subunit in primary cultured rat hippocampus cells.
To study the mechanism of action of the novel anticonvulsant and mood stabilizer lamotrigine, we used cDNA array to generate an expression profile of lamotrigine-regulated genes in primary cultured rat hippocampus cells. Gene expression was analyzed using Atlas Rat 1.2 Arrays of approximately 1200 genes. Total RNA was isolated from control and cells treated with lamotrigine at 0.1 mM for one week and reverse-transcribed to cDNA labeled with 32P-dATP. The cDNA probes were hybridized with two identical cDNA array membranes. After comparing hybridized signals between these two membranes, we found that chronic treatment with lamotrigine increased the expression of eight genes and decreased the expression of six genes. One of the upregulated genes is GABA-A receptor beta subunit. This increase in GABA-A receptor beta3 subunit expression was further confirmed by Northern blotting analysis. In situ hybridization revealed that chronic treatment with lamotrigine increased GABA-A receptor beta3 subunit gene expression in CA1, CA3 and dentate gyrus of rat hippocampus. Our findings indicate that lamotrigine may effect GABA-A receptor regulated functions in the central nervous system.
Wang
Jun Feng
JF
Department of Psychiatry and Behavioural Neurosciences, McMaster University, 1200 Main Street West, Hamilton, Ontario, Canada L8N 3Z5. wangjf@mcmaster.ca
Sun
Xiujun
X
Chen
Biao
B
Young
L Trevor
LT
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D015152:Blotting, Northern; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000187:drug effects*; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D017403:In Situ Hybridization; D000077213:Lamotrigine; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000096:biosynthesis / Q000302:isolation & purification; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000235:genetics; D014227:Triazines / Q000494:pharmacology*
D000927:Anticonvulsants; D012333:RNA, Messenger; D011963:Receptors, GABA-A; D014227:Triazines; D000077213:Lamotrigine