The microRNA-455 Null Mouse Has Memory Deficit and Increased Anxiety, Targeting Key Genes Involved in Alzheimer's Disease.
Tracey E SwinglerLingzi NiuMatthew G PontifexDavid VauzourIan M ClarkPublished in: International journal of molecular sciences (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.
Keyphrases
- cell proliferation
- long non coding rna
- poor prognosis
- long noncoding rna
- wild type
- weight gain
- crispr cas
- working memory
- high fat diet induced
- binding protein
- end stage renal disease
- body mass index
- cerebrospinal fluid
- newly diagnosed
- induced apoptosis
- chronic kidney disease
- pi k akt
- insulin resistance
- transcription factor
- type diabetes
- signaling pathway
- sleep quality
- cognitive decline
- cerebral ischemia
- white matter
- skeletal muscle
- drug delivery
- blood brain barrier
- multiple sclerosis
- physical activity
- resting state
- amino acid