Author:
Hu Yan,Meng Buliang,Yin Saige,Yang Meifeng,Li Yilin,Liu Naixin,Li Shanshan,Liu Yixiang,Sun Dandan,Wang Siyu,Wang Yinglei,Fu Zhe,Wu Yutong,Pang Ailan,Sun Jun,Wang Ying,Yang Xinwang
Abstract
Abstract
Background
Due to the complexity of the mechanisms involved in epileptogenesis, the available antiseizure drugs (ASDs) do not meet clinical needs; hence, both the discovery of new ASDs and the elucidation of novel molecular mechanisms are very important.
Methods
BALB/c mice were utilized to establish an epilepsy model induced by pentylenetetrazol (PTZ) administration. The peptide HsTx2 was administered for treatment. Primary astrocyte culture, immunofluorescence staining, RNA sequencing, identification and quantification of mouse circRNAs, cell transfection, bioinformatics and luciferase reporter analyses, enzyme-linked immunosorbent assay, RNA extraction and reverse transcription–quantitative PCR, Western blot and cell viability assays were used to explore the potential mechanism of HsTx2 via the circ_0001293/miR-8114/TGF-β2 axis.
Results
The scorpion venom peptide HsTx2 showed an anti-epilepsy effect, reduced the inflammatory response, and improved the circular RNA circ_0001293 expression decrease caused by PTZ in the mouse brain. Mechanistically, in astrocytes, circ_0001293 acted as a sponge of endogenous microRNA-8114 (miR-8114), which targets transforming growth factor-beta 2 (TGF-β2). The knockdown of circ_0001293, overexpression of miR-8114, and downregulation of TGF-β2 all reversed the anti-inflammatory effects and the influence of HsTx2 on the MAPK and NF-κB signaling pathways in astrocytes. Moreover, both circ_0001293 knockdown and miR-8114 overexpression reversed the beneficial effects of HsTx2 on inflammation, epilepsy progression, and the MAPK and NF-κB signaling pathways in vivo.
Conclusions
HsTx2 suppressed PTZ-induced epilepsy by ameliorating inflammation in astrocytes via the circ_0001293/miR-8114/TGF-β2 axis. Our results emphasized that the use of exogenous peptide molecular probes as a novel type of ASD, as well as to explore the novel endogenous noncoding RNA-mediated mechanisms of epilepsy, might be a promising research area.
Graphical Abstract
Funder
Key Project of Yunnan Applied Basic Research Project-Kunming Medical University Union Foundation
Applied Research Foundation of Diagnosis and Treatment Center of Nervous System Diseases of Yunnan Province
Applied Basic Research Project of Yunan Province
Project of Yunnan Applied Basic Research Project-Kunming Medical University Union Foundation
National Natural Science Foundation of China
Publisher
Springer Science and Business Media LLC
Subject
Cellular and Molecular Neuroscience,Neurology,Immunology,General Neuroscience
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