RESUMO
This study aimed to investigate the expression of autophagy-related proteins in a mouse model of neuromyelitis optica (NMO). Mice were assigned to one of four groups: an animal experimental model group (NMO-EAE group, given with exogenous IL-17A), Interleukin-17 monoclonal antibody intervention group (NMO-EAE_0IL17inb), No exogenous interleukin-17 enhanced immune intervention group (NMO-EAE_0IL17), and a control group. Behavioral scores were assessed in each group, and the protein expressions of sequestosome 1 (P62), Beclin-1, the mammalian target of rapamycin (mTOR), phosphoinositide 3-kinase (PI3K-I), and LC3II/LC3I were detected using Western blotting. In the NMO-EAE_0IL17 group, the expression of Beclin-1 decreased, the LC3II/LC3I ratio was lower, and the expressions of P62, mTOR, and PI3K-I increased; after administration of IL-17A inhibitor into the brain tissue, however, the expression of Beclin-1 increased significantly, along with the LC3II/LC3I ratio, while the expressions of P62, mTOR and PI3K-I protein decreased significantly. In terms of behavioral scores, the scores of optic neuritis and myelitis were more serious, onset occurred earlier and the progress was faster, after the administration of IL-17A. In the mechanism of NMO animal model, IL-17A may regulate autophagy and affect the disease process through the activation of the PI3K-mTOR signaling pathway.
Assuntos
Neuromielite Óptica , Camundongos , Animais , Interleucina-17 , Proteínas Relacionadas à Autofagia , Proteína Beclina-1/genética , Proteína Beclina-1/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo , Mamíferos/metabolismoRESUMO
Postoperative cognitive dysfunction (POCD) affects a substantial number of aged individuals. Although advanced age has been regarded as the only independent risk factor for cognitive decline following anesthesia and surgery, the exact cellular and molecular mechanisms remain poorly understood. Histone deacetylase 3 (HDAC3), an epigenetic regulator of memory plays an important role in age-dependent disease. In this study, we investigated the role of HDAC3 in POCD using a laparotomy mouse model. The results showed that the level of HDAC3 in the dorsal hippocampus (DH) was elevated in aged mice compared with young mice. The surgery impaired the spatial-temporal memory in aged mice, as indicated in the object location memory (OLM) and temporal order memory (TOM) tests. Model mice also exhibited increased expression of HDAC3 protein and decreased levels of dendritic spine density and synaptic plasticity-related proteins in the DH. Selectively blocking HDAC3 in the DH of aged mice reversed spatial-temporal memory impairment induced by surgery and restored dendritic spine density and synaptic plasticity-related proteins in the DH. Overexpression of HDAC3 by adeno-associated virus in the DH of young mice mimicked the behavioral deficits induced by anesthesia and surgery. Our results indicated that HDAC3 negatively regulates spatial-temporal memory in aged mice after anesthesia and surgery. Targeting HDAC3 might represent a potential therapy to avoid POCD.
Assuntos
Disfunção Cognitiva , Complicações Cognitivas Pós-Operatórias , Animais , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/metabolismo , Hipocampo/metabolismo , Histona Desacetilases/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Plasticidade NeuronalRESUMO
Recycling waste tires through pyrolysis technology generates refractory wastewater, which is harmful to the environment if not disposed properly. In this study, a combined process of coagulation detoxification and biodegradation was used to treat tire pyrolysis wastewater. Organics removal characteristics at the molecular level were investigated using electrospray ionization (ESI) coupled with Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS). The results showed that nearly 90% of the organic matter from the wastewater was removed through the process. Preference of the two coagulants for different classes of organics in tire pyrolysis wastewater was observed. The covalently bound inorganic-organic hybrid coagulant (CBHyC) used in this work had a complementary relationship with biodegradation for the organics removal: this coagulant reduced toxicity and enhanced the biodegradation by preferentially removing refractory substances such as lignin with a high degree of oxidation (O/C > 0.3). This study provides molecular insight into the organics of tire pyrolysis wastewater removed by a combined treatment process, supporting the advancement and application of waste rubber recycling technology. It also contributes to the possible development of an effective treatment process for refractory wastewater.