MRNA differential display identification of thyroid hormone‐responsive protein (THRP) gene in association with early phase of long‐term potentiation

Abstract

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.

Dorsal Hippocampal Administration of Triiodothyronine Enhances Long‐Term Memory for Trace Cued and Delay Contextual Fear Conditioning in Rats

“…In addition, thyroid hormone can stimulate synaptosomal Ca 2+ uptake (49,50) and activate intracellular signalling pathways, such as those mediated by protein kinase C, protein kinase A and extracellular signalregulated kinases ⁄ mitogen-activated protein kinases (51), as well as regulate some gene transcription factors (21,52), which are all thought to be involved in intracellular signalling that supports synaptic plasticity and learning and memory. Direct infusion of T3 into the dentate gyrus region of the hippocampus of euthyroid rats produces long-term potentiation phenomena (53), the most dominant model of synaptic plasticity (54), supporting the idea that T3 administration activates a chain of events linking learning and memory.…”

Effects of subchronic aluminum exposure on spatial memory, ultrastructure and L-LTP of hippocampus in rats

“…Especially, the thickness of the PSD represented synaptic efficacy (Jing, 2004); synaptic curvature reflected a morphological index of synaptic plasticity representing the different function of synapses such as the neuron transmitter release signs and the configuration changes in postsynaptic receptors (Markus and Petit, 1989). Subtle changes in synaptic structure can alter biophysical properties of synapses (Tang et al, 2001). In addition, another research revealed that synaptic plasticity referred to the change of synaptic efficacy, the changes of synaptic transmission efficacy are usually followed by the structural modification of synapses (Lu, 2008).…”

Experimentally Induced Hyperthyroidism Disrupts Hippocampal Long-Term Potentiation in Adult Rats

“…Thyroid hormone treatment failed to normalize these two neurophysiological abnormalities observed in hypothyroid animals [42], as expected from our finding that thyroxine treatment depressed electrical responses within the DG. Although neither the expression of NMDARs nor DG histology was examined in the present study, we believe that one possible mechanism by which the findings of impaired LTP and spatial learning may be explained is through the change in expression of different NMDAR subunits, including NR1 mRNA or NR2B mRNA [38,52,53]. Given that PTP was also affected by thyroxine application, it seems worth considering that some of the effects of thyroxine may involve presynaptic as well as postsynaptic mechanisms.…”