The microRNA-455 null mouse has memory deficit and increased anxiety, targeting key genes involved in Alzheimer’s disease

Swingler, Tracey E., Niu, Lingzi, Pontifex, Matthew G., Vauzour, David and Clark, Ian M. (2022) The microRNA-455 null mouse has memory deficit and increased anxiety, targeting key genes involved in Alzheimer’s disease. International Journal of Molecular Sciences, 23 (1). ISSN 1661-6596

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Abstract

The complete molecular mechanisms underlying the pathophysiology of Alzheimer’s disease (AD) remain to be elucidated. Recently, microRNA-455-3p has been identified as a cir-culating biomarker of early AD, with increased expression in post-mortem brain tissue of AD patients. MicroRNA-455-3p also directly targets and down-regulates APP, with the overexpres-sion of miR-455-3p suppressing its toxic effects. Here, we show that miR-455-3p expression de-creases with age in the brains of wild-type mice. We generated a miR-455 null mouse utilising CRISPR-Cas9 to explore its function further. Loss of miR-455 resulted in increased weight gain, potentially indicative of metabolic disturbances. Furthermore, performance on the novel object recognition task diminished significantly in miR-455 null mice (p = 0.004), indicating deficits in recognition memory. A slight increase in anxiety was also captured on the open field test. BACE1 and TAU were identified as new direct targets for miR-455-3p, with overexpression of miR-455-3p leading to a reduction in the expression of APP, BACE1 and TAU in neuroblastoma cells. In the hippocampus of miR-455 null mice at 14 months of age, the levels of protein for APP, BACE1 and TAU were all increased. Such findings reinforce the involvement of miR-455 in AD progression and demonstrate its action on cognitive performance.

Item Type: Article
Additional Information: Funding Information: Funding: T.E.S. was funded by a Dunhill Medical Trust Programme grant (number R476/0516); L.N. was funded by Action Arthritis and Funds for Women Graduates (number GA-00842).
Uncontrolled Keywords: app,alzheimer’s disease,anxiety,bace1,knockout,memory,mir-455,microrna,novel object recognition,tau,catalysis,molecular biology,spectroscopy,computer science applications,physical and theoretical chemistry,organic chemistry,inorganic chemistry ,/dk/atira/pure/subjectarea/asjc/1500/1503
Faculty \ School: Faculty of Science > School of Biological Sciences
Faculty of Medicine and Health Sciences > Norwich Medical School
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Depositing User: LivePure Connector
Date Deposited: 04 Jan 2022 14:30
Last Modified: 13 Jan 2022 01:12
URI: https://ueaeprints.uea.ac.uk/id/eprint/82881
DOI: 10.3390/ijms23010554

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