MiR-34a deficiency enhances nucleic acid sensing and type I IFN signaling in a mouse model of Alzheimer's disease
Yang, J.; Tsourdinis, G. E.; Holas, C.; Maienschein-Cline, M.; Lalonde, R.; Fukuchi, K.
Show abstract
MiR-34a is implicated in aging, cell senescence, inflammation, and neurodegenerative diseases. In order to investigate the role of miR-34a in Alzheimers disease (AD), we produced an AD mouse model, Tg-SwDI mice, with whole body/constitutive miR-34a knockout (KO). MiR-34a KO improved long-term memory in Tg-SwDI mice, which was associated with decreases in the ratio of insoluble A{beta}42 to A{beta}40 and with increases in soluble and insoluble A{beta}40 in the cerebral cortex. Anti-Iba1 immunofluorescence revealed increases in activated microglia. Bulk RNA-sequencing of the hippocampus followed by a gene set enrichment analysis (Enrichr) identified "cellular response to type I interferon" and "type I interferon signaling pathway" as the most prominent gene sets in miR-34a KO Tg-SwDI mice compared to miR-34a wild-type Tg-SwDI mice. Many interferon-stimulated genes (ISGs) that characterize interferon responsive microglia (IRM) were upregulated in miR-34a KO Tg-SwDI mice. MiR-34a knockdown strongly enhanced ISGs expression in TLR7 ligand-stimulated BV2 microglia. These results suggest that miR-34a inhibits the transition of microglia to the IRM state that may modulate synaptic and cognitive functions in neurodegenerative diseases and aging.
Matching journals
The top 14 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Dual-specificity protein phosphatase 6 (DUSP6) overexpression reduces amyloid load and improves memory deficits in male 5xFAD mice 97%
- Plcg2M28L interacts with high fat-high sugar diet to accelerate Alzheimers disease-relevant phenotypes in mice 96%
- Evaluation of CB2R expression and pyridine-based radiotracers in brains from a mouse model of Alzheimer's disease 95%
Similar papers in this journal
- Lack of p62 impairs glycogen aggregation and exacerbates pathology in a mouse model of myoclonic epilepsy of Lafora 95%
- NRF2 deficiency promotes ferroptosis of astrocytes mediated by oxidative stress in Alzheimer's disease 95%
- Increased levels of circulating methylglyoxal have no consequence for cerebral microvascular integrity and cognitive function in young healthy mice 94%
Similar papers in this journal
- 25-Hydroxycholesterol amplifies microglial IL-1β production in an apoE isoform-dependent manner 96%
- Pathological Mechanisms of Motor Dysfunction in Familial Danish Dementia: Insights from a Knock-In Rat Model 95%
- Changes in lipid metabolism track with the progression of neurofibrillary pathology in tauopathies. 95%
Similar papers in this journal
- Perinatal IL-1-induced Inflammation Suppresses Tbr2+ Intermediate Progenitor Cell Proliferation in the Developing Hippocampus accompanied by Long-Term Behavioral Deficits 95%
- Early-life obesogenic environment integrates immunometabolic and epigenetic signatures governing neuroinflammation 95%
- FINCA disease mouse model exhibits altered behaviour and immune response 94%
Similar papers in this journal
- Oxytocin administration in neonates shapes the hippocampal circuitry and restores social behavior in a mouse model of autism. 95%
- Ucp2-dependent microglia-neuronal coupling controls ventral hippocampal circuit function and anxiety-like behavior 95%
- Scanning ultrasound-mediated memory and functional improvements do not require amyloid-β reduction 95%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.