MICRORNA-138 IMPAIRS LEARNING AND MEMORY BY TARGETING ANK1

Abstract

Alzheimer's disease (AD) is characterized by brain deposition of the amyloid beta-protein (A β) and Tau hyperphosphorylation that are associated with cognitive impairment and dementia. Many factors are involved in the pathologies of AD, like protein kinase, transcriptional factors, etc. While some evidence has been found for understanding the genetic and molecular mechanisms of AD, the role of small noncoding RNAs in occurrence and development of AD remains to be investigated. Using the Morris water maze, contextual fear conditioning, long-term potentiation recording in extracorporeal hippocampus slices, and Golgi staining, we report the roles of mir-138 in C57BL/6J mice and AD mice. Using real-time polymerase chain reaction, dual luciferase reporter assay and western blotting experiments, we further determined the target of the mir-138. Overexpression of mir-138 induces Tau hyperphosphorylation and decreases the number of dendrite spines in control mice model. In contrast, inhibition of mir-138 ameliorates these changes in AD mice. Furthermore, we confirm that ankyrin 1 (ANK1) is a direct target of miR-138, and supplement of ANK1 substantially reduces tau phosphorylation induced by miR-138. small noncoding RNAs, like mir-138, may be a therapeutic potential target for reversing cognitive impairments of AD.