| Summary: | 碩士 === 慈濟大學 === 分子生物暨人類遺傳學系碩士班 === 99 === Methyl-CpG-binding protein 2 (MeCP2), highly expressed in neurons, plays an important role in various neuronal functions such as neuronal differentiation, maturation, and synaptic plasticity. MeCP2 functions as a transcriptional regulator by binding to methylated genes and subsequently leading to chromatin remodeling and inhibition of transcription. MECP2 mutation has been known to be associated with Rett syndrome that is a progressive neurodevelopment disorder with common phenotype of mental retardation. Previous in vitro studies have found MeCP2 phosphorylation can be induced by neuronal activity. Recent studies showed that phosphorylation of MeCP2 at serine 421 (S421) caused by neuronal activity, on the other hand, phosphorylation of MeCP2 at serine 80 (S80) was observed in the resting neurons. The mechanism of MeCP2 phosphorylation underlying learning and memory remains unclear. Therefore, in this thesis research, fear conditioning paradigm was used to investigate the change of expression and phosphorylation levels of MeCP2 in the hippocampus after training. Results demonstrated that immediate expression level of phospho-MeCP2 at S421 of the trace fear conditioning (TFC) group was significantly higher than delay fear conditioning (DFC) and naive groups in the all examined regions of the right hippocampus, TFC 、 DFC group and Naïve group were higher in the denate gyrus of the left hippocampus；phosphorylation level at S80 of the TFC group was not significantly different among groups in the left hippocampus but higher in the all regions of the right hippocampus after training of few seconds. Phosphorylation levels and regions of MeCP2 also changed at later time points for the three groups. The results indicate that immediately increased phosphorylation of MeCP2 in the right hippocampal region(s) of TFC group may help regulate immediate early genes expression for trace learning. Changes of phosphorylation levels in all the hippocampal regions at later time points implied the MeCP2-mediated genes expression was required for the following events of memory formation. Further study on the expression and functions of downstream genes will help delineate molecular pathway(s) that transmit and form fear memory.
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