mRNA differential display identification of thyroid hormone-responsive protein (THRP) gene in association with early phase of long-term potentiation.
The process of long-term potentiation (LTP) consists of the early induction and late maintenance phases. Few studies have examined the cellular mechanisms underlying these two phases; their respective mRNA expression profiles have not yet been elucidated. Here we used the technique of PCR differential display to identify genes that are differentially expressed between the early and late phases of LTP in vivo. Our results indicated that the cDNA fragment corresponding to one mRNA with preferentially increased expression during the early, but not late, phase of LTP encodes the rat thyroid hormone-responsive protein (THRP) gene. In situ hybridization analysis confirmed the results obtained from the PCR differential display. Prior NMDA receptor blockade with MK801 prevented induction of LTP and decreased THRP mRNA expression in the dentate gyrus, as assayed by quantitative RT-PCR analysis. THRP antisense oligonucleotide treatment before tetanic stimulation also prevented induction of LTP. However, when THRP antisense oligonucleotide was administered after induction of LTP, it did not affect expression and maintenance of LTP. THRP is known to be responsive to thyroid hormone. Our results indicate that direct thyroid hormone (T3) injection into the dentate gyrus produces a long-lasting enhancement of synaptic efficacy of these neurons. T3 injection also markedly increased THRP mRNA expression in the dentate gyrus. Taken together, our results suggest that THRP mRNA expression plays an important role in the early phase, but not the late phase, of LTP and that both THRP and thyroid hormone are involved in synaptic plasticity in hippocampal neurons.
Tang
Y P
YP
Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan, Republic of China.
Ma
Y L
YL
Chen
S K
SK
Lee
E H
EH
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D020869:Gene Expression Profiling; D018398:Homeodomain Proteins / Q000235:genetics*; D017403:In Situ Hybridization; D017774:Long-Term Potentiation / Q000187:drug effects / Q000235:genetics*; D008297:Male; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013569:Synapses / Q000187:drug effects / Q000502:physiology; D013997:Time Factors; D014284:Triiodothyronine / Q000494:pharmacology
C109099:Abi2 protein, rat; D048868:Adaptor Proteins, Signal Transducing; D018691:Excitatory Amino Acid Antagonists; D018398:Homeodomain Proteins; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D014284:Triiodothyronine; D016291:Dizocilpine Maleate