Effects of Inhibiting lncRNA H19 Expression on Neuroinflammation and Cognitive Function in Vascular Dementia Models

Haixiao BAI; Huan WANG; Xinfei DUAN; Pingping FANG; Xiao LI; Jundong JIA

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Haixiao BAI, Huan WANG, Xinfei DUAN, Pingping FANG, Xiao LI, Jundong JIA. Effects of Inhibiting lncRNA H19 Expression on Neuroinflammation and Cognitive Function in Vascular Dementia Models[J]. Journal of Kunming Medical University.

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Effects of Inhibiting lncRNA H19 Expression on Neuroinflammation and Cognitive Function in Vascular Dementia Models

1.
Department of Critical Care Medicine
2.
Department of Neurology
3.
Department of General Practice，Handan Central Hospital，Handan Hebei 056000，China

Abstract

Abstract

Objective To explore the effects of long non-coding RNA （lncRNA） H19 on neuroinflammation and cognitive function in a vascular dementia （VD） model. Methods A VD mouse model was established by bilateral common carotid artery occlusion. Forty-eight mice were randomly and equally divided into four groups: sham surgery group, model group, NC group, and shRNA-H19 group. The sham surgery group underwent no ligation. Following successful model establishment, AAV2/1-shRNA-vehicle and AAV2/1-shRNA-H19 were injected into the brain of mice in the NC group and shRNA-H19 group, respectively. Cognitive levels was assessed useing Morris water maze test. Pathological changes in the hippocampal CA1 region and neuronal injury were observed by HE and Nissl staining. Neuronal apoptosis was detected by TUNEL staining. Levels of tumor necrosis factor-α （TNF-α）, interleukin （IL）-1β, and IL-6 in hippocampal tissue were measured by enzyme-linked immunosorbent assay （ELISA）. Expression of ionized calcium-binding adapter molecule-1 （Iba-1） protein in the hippocampal CA1 region was detected by immunofluorescence staining. Expression of H19, B-cell lymphoma-2 （Bcl-2）, cleaved caspase-3, toll-like receptor 4 （TLR4）, and nuclear factor-kappa B （NF-κB） protein and/or mRNA in hippocampal tissue were detected by quantitative real-time polymerase chain reaction （qRT-PCR） and/or Western blot. Results Compared with the model group, shRNA-H19 mice exhibited improved cognitive function （P < 0.05）, reduced pathological changes and neuronal injury in the hippocampal CA1 region, elevated Bcl-2 levels in hippocampal tissue, and decreased neuronal apoptosis rate, H19, TNF-α, IL-1β, IL-6, Iba-1, cleaved caspase-3, TLR4, and NF-κB p-p65/NF-κB p65 levels （P < 0.05）. The NC group showed no significant differences in the above indicators （P > 0.05）. Conclusion Inhibition of H19 expression in hippocampal tissue ameliorates neuroinflammation and improve cognitive function in VD mice, inhibits neuronal apoptosis and microglial infiltration in the hippocampal CA1 region. The underlying mechanism may be related to downregulation of the TLR4/NF-κB p65 signaling pathway.
- Vascular dementia,
- Long non-coding RNA H19,
- Neuronal apoptosis,
- Neuroinflammation,
- TLR4/NF-ΚB P65 pathway,
- Mice

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References(19)

References

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