miR-107-5p ameliorates neurological damage, oxidative stress, and immune responses in mice with Alzheimer's disease by suppressing the Toll-like receptor 4 (TLR4)/nuclear factor-kappaB(NF-κB) pathway.
Kaohsiung J Med Sci
; 40(2): 119-130, 2024 Feb.
Article
in En
| MEDLINE
| ID: mdl-38305705
ABSTRACT
Alzheimer's disease (AD) is a progressively debilitating neurodegenerative condition primarily affecting the elderly. Emerging research suggests that microRNAs (miRNAs) play a role in the development of AD. This study investigates the impact of miR-107-5p on neurological damage, oxidative stress, and immune responses in AD. We utilized APP/PS1 mice as AD mouse models and C57BL/6 J mice as controls. AD mice received treatment with agomir miR-107-5p (to overexpress miR-107-5p) or BAY11-7082 (an NF-κB pathway inhibitor). We evaluated learning and memory abilities through the Morris water maze test. Histopathological changes, hippocampal neuron distribution, and apoptosis were assessed using hematoxylin-eosin, Nissl, and TUNEL staining. Reactive oxygen species (ROS) levels, amyloid-Aß (Aß1-40/42) contents, and inflammatory factors (TNF-α, IL-6, IL-1ß) in hippocampal tissues were measured using ROS kits and enzyme-linked immunosorbent assay (ELISA). Microglial activation in hippocampal tissues was observed under a fluorescence microscope. miR-107-5p's binding to TLR4 was predicted via the TargetScan database and confirmed through a dual-luciferase assay. miR-107-5p expression, along with TLR4, APOE, and TREM2 in hippocampal tissue homogenate, and NF-κB p65 protein expression in the nucleus and cytoplasm were assessed via RT-qPCR and Western blot. Overexpression of miR-107-5p ameliorated hippocampal neurological damage, oxidative stress, and immune responses. This was evidenced by improved enhanced learning/memory abilities, reduced Aß1-40 and Aß1-42 levels, diminished neuronal injuries, decreased ROS and TNF-α, IL-6, and IL-1ß levels, increased APOE and TREM2 levels, and suppressed microglial activation. miR-107-5p directly targeted and inhibited TLR4 expression, leading to reduced nuclear translocation of NF-κB p65 in the NF-κB pathway. Inhibition of the NF-κB pathway similarly improved neurological damage, oxidative stress, and immune response in AD mice. miR-107-5p exerts its beneficial effects by suppressing the TLR4/NF-κB pathway, ultimately ameliorating neurological damage, oxidative stress, and immune responses in AD mice.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
MicroRNAs
/
Alzheimer Disease
Type of study:
Prognostic_studies
Limits:
Animals
/
Humans
Language:
En
Journal:
Kaohsiung J Med Sci
Journal subject:
MEDICINA
Year:
2024
Document type:
Article
Affiliation country:
China
Country of publication:
China