RESUMO
BACKGROUND: Neuroinflammation contributes to both epileptogenesis and the associated neurodegeneration, so regulation of inflammatory signaling is a potential strategy for suppressing epilepsy development and pathological progression. Exosomes are enriched in microRNAs (miRNAs), considered as vital communication tools between cells, which have been proven as potential therapeutic method for neurological disease. Here, we investigated the role of miR129-5p-loaded mesenchymal stem cell (MSC)-derived exosomes in status epilepticus (SE) mice model. METHODS: Mice were divided into four groups: untreated control (CON group), kainic acid (KA)-induced SE groups (KA group), control exosome injection (KA + Exo-con group), miR129-5p-loaded exosome injection (KA + Exo-miR129-5p group). Hippocampal expression levels of miR129-5p, HMGB1, and TLR4 were compared among groups. Nissl and Fluoro-jade B staining were conducted to evaluate neuronal damage. In addition, immunofluorescence staining for IBA-1 and GFAP was performed to assess glial cell activation, and inflammatory factor content was determined by ELISA. Hippocampal neurogenesis was assessed by BrdU staining. RESULTS: The expression of HMGB1 was increased after KA-induced SE and peaking at 48 h, while hippocampal miR129-5p expression decreased in SE mice. Exo-miR129-5p injection reversed KA-induced upregulation of hippocampal HMGB1 and TLR4, alleviated neuronal damage in the hippocampal CA3, reduced IBA-1 + and GFAP + staining intensity, suppressed SE-associated increases in inflammatory factors, and decreased BrdU + cell number in dentate gyrus. CONCLUSIONS: Exosomes loaded with miR129-5p can protect neurons against SE-mediated degeneration by inhibiting the pro-inflammatory HMGB1/TLR4 signaling axis.
Assuntos
Exossomos , Proteína HMGB1 , MicroRNAs , Estado Epiléptico , Animais , Camundongos , Bromodesoxiuridina/efeitos adversos , Bromodesoxiuridina/metabolismo , Exossomos/metabolismo , Hipocampo/metabolismo , Proteína HMGB1/genética , Proteína HMGB1/metabolismo , Ácido Caínico/efeitos adversos , Ácido Caínico/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Doenças Neuroinflamatórias , Convulsões/genética , Estado Epiléptico/induzido quimicamente , Estado Epiléptico/genética , Estado Epiléptico/metabolismo , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismoRESUMO
The field of molecular catalysts places a strong emphasis on the connection between the ligand structure and its catalytic performance. Herein, we changed the type of coordinated nitrogen atom in pentadentate amine-pyridine ligands to explore the impact of its hybridization form on the water oxidation performance of copper complexes. In the electrochemical tests, the copper complex bearing dipyridine-triamine displayed an apparently higher rate constant of 4.97 s-1, while the copper complex with tripyridine-diamine demonstrated overpotential reduction by 56 mV and better long-term electrolytic stability.
