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Article

The microRNA-455 Null Mouse Has Memory Deficit and Increased Anxiety, Targeting Key Genes Involved in Alzheimer’s Disease

1
School of Biological Sciences, University of East Anglia, Norwich NR4 7TJ, UK
2
Norwich Medical School, University of East Anglia, Norwich NR4 7TJ, UK
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editors: Masaru Tanaka and Lydia Giménez-Llort
Int. J. Mol. Sci. 2022, 23(1), 554; https://doi.org/10.3390/ijms23010554
Received: 10 November 2021 / Revised: 24 December 2021 / Accepted: 30 December 2021 / Published: 5 January 2022
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 circulating 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 overexpression of miR-455-3p suppressing its toxic effects. Here, we show that miR-455-3p expression decreases 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. View Full-Text
Keywords: Alzheimer’s disease; microRNA; miR-455; knockout; APP; TAU; BACE1; novel object recognition; memory; anxiety Alzheimer’s disease; microRNA; miR-455; knockout; APP; TAU; BACE1; novel object recognition; memory; anxiety
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MDPI and ACS Style

Swingler, T.E.; Niu, L.; Pontifex, M.G.; Vauzour, D.; Clark, I.M. The microRNA-455 Null Mouse Has Memory Deficit and Increased Anxiety, Targeting Key Genes Involved in Alzheimer’s Disease. Int. J. Mol. Sci. 2022, 23, 554. https://doi.org/10.3390/ijms23010554

AMA Style

Swingler TE, Niu L, Pontifex MG, Vauzour D, Clark IM. The microRNA-455 Null Mouse Has Memory Deficit and Increased Anxiety, Targeting Key Genes Involved in Alzheimer’s Disease. International Journal of Molecular Sciences. 2022; 23(1):554. https://doi.org/10.3390/ijms23010554

Chicago/Turabian Style

Swingler, Tracey E., Lingzi Niu, Matthew G. Pontifex, David Vauzour, and Ian M. Clark. 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, no. 1: 554. https://doi.org/10.3390/ijms23010554

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