The role of microRNA‐195 in age‐dependent impairment of cognitive function

Abstract

MicroRNA‐195 (miR‐195) is a member of the miR‐16/15/195/424/497 family. It is abundantly expressed in normal tissue, including the brain. Recently, an anti‐senescence role of miR‐195 was reported. However, its significance in age‐associated change in cognitive function has not been properly characterized. Using a tamoxifen‐inducible miR‐195 knock out (miR‐195+/− KO) mice based on the Cre‐loxP system, we compared in this study temporal profiling of cognitive functions in the mice at age of 3, 6, 9, 12 and 15 months to their wild type (WT) control. The Morris water maze was performed to evaluate cognitive function, sequential magnetic resonance imaging (MRI), coupled with diffusion tensor imaging (DTI) acquisition was carried out to evaluate the brain connectivity. In both WT and miR‐195+/− KO mice, the slope of time latency to reach the hidden platform in the water maze during the 5 consecutive training days became gentle, but not different between the two groups, suggesting there is no difference in the age dependency of learning in both groups. However, at 12 and 15 months of age, both preference and time spending in the target quadrant were notably shorter in miR‐195+/− KO mice, compared to the WT mice. There is no difference in total distance traveled and velocity between WT and miR‐195+/− KO mice during the tests, suggesting the locomotor ability was not affected in the KO mice. Next generation sequence analysis further revealed that among the target genes of miR‐195, expression of both Plexin‐A1 and its ligand, Sema3A, were significantly increased in the hippocampus of miR‐195+/− KO mice. Sema3A binds with Plexin‐A1 to induce neuronal apoptosis. Tractographic analysis based on MRI/DTI of forebrain image revealed no apparent change in connectivity between the hippocampus and cortical areas of both WT and miR‐195+/− KO mice at age of 12 or 15 months. Taken together, these data indicate that while miR‐195 may not play a permissive role in spatial learning, it is crucial for memory retrieving during aging process. This may mediate via suppression of neuronal apoptosis in the hippocampus when changes in hippocampal‐cortical neural connectivity are not yet bechanced.Support or Funding InformationMOST106‐2314‐B182A‐003 from the Ministry of Science and Technology, Taiwan; OMRPG8G0011 from Chang Gung Medical Foundation, TaiwanThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.