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首页> 外文期刊>Cellular Physiology and Biochemistry >Expression of Amyloid-Associated miRNAs in Both the Forebrain Cortex and Hippocampus of Middle-Aged Rat
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Expression of Amyloid-Associated miRNAs in Both the Forebrain Cortex and Hippocampus of Middle-Aged Rat

机译：淀粉样蛋白相关的miRNA在中年大鼠前皮质和海马中的表达

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biBackground /i/bAging is associated with the gradual cognitive decline and shows the typical senile plaque formation in the brain, which results from the aggregation of beta amyloid (Aβ) peptide following the abnormal proteolytic processing of amyloid precursor protein (APP) by β-secretase (BACE1) and γ-secretase. Accumulating evidence indicates that several microRNAs (miRNAs) are involved in the Alzheimer's disease (AD) by regulating the expression of APP and BACE1 proteins. However, the cognitive ability and the expression profile of the APP- and BACE1-associated miRNAs in the middle-aged population are largely unknown. biMethods /i/bThe learning and memory ability in rats were determined by Morris Water Maze test. The protein levels of APP and BACE1 were detected by western blotting. The quantitative polymerase chain reaction was used to identify the miRNAs levels in forebrain cortex and the hippocampus. biResults /i/bMiddle-aged rats have declined learning ability without changes in the memory ability, and increased APP and BACE1 protein expression in the forebrain cortex. Computational analysis using Targetscan and Pictar databases reveals that totally 4 predicted miRNAs have conserved binding site with APP, namely imiR-106b, -17-5p, -153, -101/i. All of them showed decreased expression in both the forebrain cortex and hippocampus. Among the 10 predicted miRNAs targeting BACE1, different expression profiles were identified in the forebrain cortex (decreased imiR-9, -19a, -135a, -15b, -16, -195, -29c, -214/i; increased imiR-124/i; no change imiR-141/i) and the hippocampus (decreased imiR-9, -15b, -16, -195, -29c, -124/i; increased imiR-19a, -135a, -214, -141/i) in the middle-aged rats compared with the young rats. biConclusion /i/bOur results provided the first evidence that middle-aged rats have begun displaying cognitive disability with abnormal expression of APP- and BACE1-related miRNAs in the hippocampus and forebrain cortex.
机译：背景 衰老与逐渐的认知能力下降有关，并显示出大脑中典型的老年斑形成，这是由于蛋白水解异常后β淀粉样蛋白（Aβ）肽的聚集所致β-分泌酶（BACE1）和＆＃947;-分泌酶处理淀粉样蛋白前体蛋白（APP）的过程。越来越多的证据表明，通过调节APP和BACE1蛋白的表达，几种微RNA（miRNA）参与了阿尔茨海默氏病（AD）。但是，在中年人群中与APP和BACE1相关的miRNA的认知能力和表达谱尚不清楚。 方法 通过Morris水迷宫测试确定大鼠的学习和记忆能力。通过蛋白质印迹法检测APP和BACE1的蛋白水平。定量聚合酶链反应用于鉴定前脑皮层和海马中的miRNA水平。 结果 中年大鼠的学习能力下降，而记忆力没有变化，前脑皮质中APP和BACE1蛋白的表达增加。使用Targetscan和Pictar数据库进行的计算分析表明，总共有4个预测的miRNA与APP保持了结合位点，即 miR-106b，-17-5p，-153，-101 。它们均在前脑皮质和海马中均表达降低。在靶向BACE1的10种预测miRNA中，在前脑皮层中鉴定出不同的表达谱（ miR-9，-19a，-135a，-15b，-16，-195，-29c，-214 降低;增加的 miR-124 ;没有变化的 miR-141 ）和海马区（降低的 miR-9，-15b，-16，-195，-29c， -124 ;与年轻大鼠相比，中年大鼠的 miR-19a，-135a，-214，-141 ）增加。 结论 我们的结果提供了第一个证据，表明中年大鼠开始表现出认知障碍，海马和前脑皮质中APP和BACE1相关miRNA的异常表达。

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