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. ORCID:, Vauzour, David ORCID: 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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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
UEA Research Groups: Faculty of Medicine and Health Sciences > Research Centres > Lifespan Health
Faculty of Medicine and Health Sciences > Research Centres > Metabolic Health
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Depositing User: LivePure Connector
Date Deposited: 04 Jan 2022 14:30
Last Modified: 06 Jun 2024 15:17
DOI: 10.3390/ijms23010554


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