| Summary: | 碩士 === 國立政治大學 === 生命科學研究所 === 98 === Our laboratory has previously identified 98 cDNA fragments by using PCR differential display from rat dorsal hippocampus that are differentially expressed between fast learners and slow learners from the water maze learning task. After sequencing and BLAST analysis, one of these cDNA fragments encodes the rat pias1 [protein inhibitor of activated STAT1 (signal transducer and activator of transcription 1)] gene. In order to determine whether pias1 gene expression is associated with spatial learning, naïve rats were randomly assigned to the trained group (with visual cues and platform been present) and the non-trained group (without the platform as the swimming control). The dorsal hippocampus from these animals was dissected out at the end of the training and was subjected to RNA and protein extraction for real-time PCR and Western blot analysis of PIAS1 expression, respectively. Results revealed that the pias1 mRNA level and protein level was both higher in the hippocampus of trained rats than non-trained rats. To further examine the role of PIAS1 involved in spatial learning and memory, the specific PIAS1 siRNA was used to knockdown the expression of PIAS1 in rat hippocampal CA1 region. We found that transfection of PIAS1 siRNA to the CA1 area impaired water maze performance, whereas transfection of the wild-type PIAS1 DNA plasmid to the CA1 area facilitated water maze performance in rats. Meanwhile, PIAS1 siRNA increased STAT1 phosphorylation at Tyr701 whereas PIAS1 WT decreased STAT1 phosphorylation at this residue. In the examination of molecular mechanism underlying PIAS1-mediated memory facilitation, we have found that transfection of the STAT1 Y701F mutant plasmid antagonized the memory-impairing effect of PIAS1 siRNA, whereas transfection of STAT1 Y701F alone facilitated spatial memory formation. These results together suggest that one of the molecular mechanisms underlying PIAS1-mediated memory facilitation is through decreased STAT1 phosphorylation at Tyr701. All these manipulations did not affect visible platform learning in rats. In addition to the well documented role of PIAS1 in the immune system, here we have been the first to demonstrate a novel role of PIAS1 involved in spatial memory formation in rats.
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