PS 07-26 PRELIMINARY COMPARISON OF CEREBRAL CORTEX miRNAs LEVELS IN HYPERTENSIVE MICE AND CONTROL SUBJECTS BY SMALL RNA SEQUENCING

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Abstract

Objective:

The pathogenesis of hypertension-related cognitive impairment has not been sufficiently clarified, current therapies for this disease are inadequate and new molecular targets are needed. MicroRNAs (miRNAs) are small, noncoding RNAs that function in complex networks to regulate protein expression. In the brain, they are involved in development and synaptic plasticity. In this study, we aimed to identify miRNAs with a differential expression in cerebral cortex from hypertensive mice and control subjects using small RNA sequencing.

Design and Method:

We used subcutaneous mini-pumps containing a concentration of Ang II that induces malignant hypertension or a saline solution for 28 days. Blood pressure was carefully monitored by a non-invasive tail-cuff method every week throughout the experiment. Spatial memory was assessed using the Morris water maze test. Total RNA was extracted from cerebral cortex. MiRNAs expression profiles were respectively determined by the sequencing analysis.

Results:

Compared to control group, the treatment of Ang II significantly raised the systolic blood pressure constant throughout the experiment in adult male mice (p < 0.05). The percentage of time spent in the target quadrant in probe test were significantly reduced in Ang II-dependent hypertensive mice(p < 0.05). 25 miRNAs were screened out to be significantly up-regulated compared to that of control mice, and 14 miRNAs were screened out to be remarkably down-regulated compared to that of control mice (P value < 0.05 and Fold change > 2). These differentially expressed miRNAs were predicted to target a large number of genes that involved in long-term potentiation, wnt signaling pathway, neurotrophin signaling pathway and other cellular bio-functions.

Conclusions:

Memory were impaired in angiotensin II-dependent hypertensive mice, the abnormal expression of several miRNAs in cerebral cortex of hypertensive mice suggests some of them may be involved in the pathogenesis of hypertension-related cognitive impairment, which requires further analysis and study.

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