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MiR‐181b inhibits P38/JNK signaling pathway to attenuate autophagy and apoptosis in juvenile rats with kainic acid‐induced epilepsy via targeting TLR4
- Publication Year :
- 2018
- Publisher :
- John Wiley and Sons Inc., 2018.
-
Abstract
- Objective To explore the role of miR-181b in alterations of apoptosis and autophagy in the kainic acid (KA)-induced epileptic juvenile rats via modulating TLR4 and P38/JNK signaling pathway. Methods Dual-luciferase reporter assay was performed to testify the targeting relationship between miR-181b and TLR4. After intracerebroventricular injection (i.c.v.) of KA, rats were injected with miR-181b agomir and TLR4 inhibitor (TAK-242). The TLR-4 activator lipopolysaccharide (LPS) was also administered into rats immediately after injection with miR-181b agomir. Quantitative real-time-polymerase chain reaction (qRT-PCR) was used for detections of miR-181b and TLR4 expressions, hematoxylin-eosin (HE) and Nissl staining for observation of the hippocampus morphological changes, and TUNEL staining for apoptosis analysis. Moreover, western blot was determined to detect TLR4 and P38/JNK pathway proteins, as well as autophagy- and apoptosis-related proteins. Results TLR4 was identified as a direct target of miR-181b using Dual-luciferase reporter assay. KA rats injected with miR-181b agomir or TAK-242 had improved learning and memory abilities, reduced seizure severity of Racine's scale, and lessened neuron injury. Additionally, miR-181b agomir or TAK-242 could significantly inhibit P38/JNK signaling, decrease LC3II/I, Beclin-1, ATG5, ATG7, ATG12, Bax, and cleaved caspases-3, but increase p62 and Bcl-2 expression. No significances were found between KA group and KA + miR-181b + LPS group. Conclusion MiR-181b could inhibit P38/JNK signaling pathway via targeting TLR4, thereby exerting protective roles in attenuating autophagy and apoptosis of KA-induced epileptic juvenile rats.
- Subjects :
- 0301 basic medicine
Male
Kainic acid
MAP Kinase Kinase 4
MAP Kinase Signaling System
p38 mitogen-activated protein kinases
ATG5
Apoptosis
Pharmacology
Hippocampus
p38 Mitogen-Activated Protein Kinases
ATG12
03 medical and health sciences
chemistry.chemical_compound
Random Allocation
0302 clinical medicine
Physiology (medical)
Autophagy
Animals
Pharmacology (medical)
Rats, Wistar
TUNEL assay
Epilepsy
Kainic Acid
Original Articles
Neuroprotection
Toll-Like Receptor 4
Psychiatry and Mental health
Disease Models, Animal
MicroRNAs
030104 developmental biology
chemistry
TLR4
Female
030217 neurology & neurosurgery
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....712946e03029637e37636d142c093158