Kindling induces the mRNA expression of methyl DNA-binding factors in the adult rat hippocampus.
We have investigated the gene expression responses of a family of methyl CpG-binding domain-containing factors (MeCP2, MBD1, MBD2, and MBD3) in the hippocampus of electrically kindled rats. Expression was examined in both amygdala- and partial perforant-pathway-kindled subjects, 24 h and 28 days following the final stimulation. In general, the responses of MBDs 2 and 3 paralleled each another, both temporally and spatially. The expression of both genes was significantly elevated in all hippocampal subfields at 24 h following either the fifth stage 5 seizure (amygdala kindling) or the 15th stimulation of the perforant pathway. This induced expression was transient, however, as the expression of both genes returned to control levels by 28 days. This pattern of response contrasted to that observed for MeCP2 and MBD1. MeCP2 displayed no change in expression either 24 h or 28 days after amygdala kindling, but did display a late-developing, significant increase in expression in the dentate gyrus at 28 days following perforant-pathway kindling. The expression of MBD1 was unchanged by partial perforant-pathway kindling, but was induced in the dentate gyrus 28 days after amygdala kindling. These results demonstrate that electrical kindling alters the hippocampal expression of methyl DNA-binding factors, but does not affect each factor equivalently. The responsive patterns observed suggest that this family of transcriptional regulators can be differentially altered in the hippocampus by seizure activity.
Division of Cell and Molecular Biology, Toronto Western Research Institute, University Health Network, 399 Bathurst Street, Toronto, Ontario, Canada M5T 2S8.
J
J
Francis
B
B
Jung
G
G
Zhang
J
J
Cheng
W
W
Ho
W M
WM
Burnham
J H
JH
Eubanks
D000679:Amygdala / Q000378:metabolism*; D000818:Animals; D002868:Chromosomal Proteins, Non-Histone; D018899:CpG Islands; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006624:Hippocampus / Q000378:metabolism*; D017403:In Situ Hybridization; D007696:Kindling, Neurologic / Q000378:metabolism*; D008297:Male; D051783:Methyl-CpG-Binding Protein 2; D019580:Perforant Pathway / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D012097:Repressor Proteins / Q000378:metabolism; D013997:Time Factors
D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; C115368:MBD2 protein; C489324:Mbd1 protein, rat; C492012:Mbd3 protein, rat; C497394:Mecp2 protein, rat; D051783:Methyl-CpG-Binding Protein 2; D012333:RNA, Messenger; D012097:Repressor Proteins