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Volume 23
Issue 1
10.3390/ijms23010554
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Article

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

by
Tracey E. Swingler
1,
Lingzi Niu
1,
Matthew G. Pontifex
2,
David Vauzour
2,*,† and
Ian M. Clark
1,*,†
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
(This article belongs to the Topic Emerging Translational Research in Neurological and Psychiatric Diseases: from In Vitro to In Vivo Models)
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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 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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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

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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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