Small RNA changes in hippocampus of transgenic murine model of tauopathy (rTg4510 mice) compared to littermate controls at asymptomatic stage (2 months) of neurodegeneration as determined by small RNA deep sequencing.. Small RNA changes in hippocampus of transgenic murine model of tauopathy (rTg4510 mice) compared to littermate controls at asymptomatic stage (2 months) of neurodegeneration as determined by small RNA deep sequencing.

The overall goal of the project is to assess whether small RNA, especially microRNA (miR) alterations in tauopathy conditions contribute to pathological changes that later lead to neurodegeneration. The animal model selected for this study is a well characterized tauopathy animal model, known as rTg4510 murine model. rTg4510 (tau) is a transgenic mouse model of human tauopathy expressing human tau containing the P301L mutation that is associated with familial frontotemporal dementia and parkinsonism linked to chromosome 17. The expression of P301L tau driven by CaMKII promoter peaks around two month-of-age and mainly in the forebrain. 2-month of age is considered the asymptomatic stage of neurodegeneration. The global expression of miRs was evaluated by small RNA sequencing in the hippocampus of tau mice at 2 months of age. The levels of several miRs were altered in the hippocampus of tau mice at 2 months. Many important candidates were further evaluated for their molecular and functional contributions to the process of neurodegeneration. Overall design: Examination of small RNAs in the hippocampus tissue of control vs tau mice at 2-month of age.

本项目的总体目标为评估小RNA——尤其是tau蛋白病（tauopathy）状态下的微小RNA（microRNA，miR）——的改变是否会促成后续引发神经退行性变的病理变化。本研究选用的动物模型为特征明确的tau蛋白病动物模型，即rTg4510小鼠模型。rTg4510（tau）是表达携带P301L突变的人tau蛋白的转基因小鼠模型，该突变与17号染色体连锁的家族性额颞叶痴呆及帕金森综合征相关。由CaMKII启动子驱动的P301L tau蛋白表达约在2月龄时达到峰值，且主要表达于前脑。2月龄被视为神经退行性变的无症状阶段。研究通过小RNA测序技术，对2月龄tau模型小鼠海马体中的miR整体表达谱进行了检测，结果显示2月龄tau模型小鼠海马体中多种miR的表达水平发生了显著改变。后续针对多个关键候选miR，深入评估了其在神经退行性变过程中的分子机制与功能贡献。总体实验设计：检测2月龄对照组小鼠与tau模型小鼠海马组织中的小RNA表达情况。