RESUMO
Fetal exposure to sevoflurane induces long-term cognitive impairment. Histone acetylation regulates the transcription of genes involved in memory formation. We investigated whether sevoflurane exposure during late-pregnancy induces neurocognitive impairment in offspring, and if this is related to histone acetylation dysfunction. We determined whether the effects could be reversed by an enriched environment (EE). Pregnant rats were exposed to 2.5% sevoflurane or control for 1, 3, or 6 h on gestational day 18 (G18). Sevoflurane reduced brain-derived neurotrophic factor (BDNF), acetyl histone H3 (Ac-H3), and Ac-H4 levels and increased histone deacetylases-2 (HDAC2) and HDAC3 levels in the hippocampus of the offspring on postnatal day 1 (P1) and P35. Long-term potentiation was inhibited, and spatial learning and memory were impaired in the 6-h sevoflurane group at P35. EE alleviated sevoflurane-induced cognitive dysfunction and increased hippocampal BDNF, Ac-H3, and Ac-H4. Exposure to 2.5% sevoflurane for 3 h during late-pregnancy decreased hippocampal BDNF, Ac-H3, and Ac-H4 in the offspring but had no effect on cognitive function. However, when the exposure time was 6 h, impaired spatial learning and memory were linked to reduced BDNF, Ac-H3, and Ac-H4, which could be reversed by EE.
Assuntos
Disfunção Cognitiva , Acetilação , Animais , Fator Neurotrófico Derivado do Encéfalo , Feminino , Hipocampo , Histonas , Aprendizagem em Labirinto , Gravidez , Ratos , SevofluranoRESUMO
Fetal exposure to sevoflurane induces long-term cognitive impairment. Histone acetylation regulates the transcription of genes involved in memory formation. We investigated whether sevoflurane exposure during late-pregnancy induces neurocognitive impairment in offspring, and if this is related to histone acetylation dysfunction. We determined whether the effects could be reversed by an enriched environment (EE). Pregnant rats were exposed to 2.5% sevoflurane or control for 1, 3, or 6 h on gestational day 18 (G18). Sevoflurane reduced brain-derived neurotrophic factor (BDNF), acetyl histone H3 (Ac-H3), and Ac-H4 levels and increased histone deacetylases-2 (HDAC2) and HDAC3 levels in the hippocampus of the offspring on postnatal day 1 (P1) and P35. Long-term potentiation was inhibited, and spatial learning and memory were impaired in the 6-h sevoflurane group at P35. EE alleviated sevoflurane-induced cognitive dysfunction and increased hippocampal BDNF, Ac-H3, and Ac-H4. Exposure to 2.5% sevoflurane for 3 h during late-pregnancy decreased hippocampal BDNF, Ac-H3, and Ac-H4 in the offspring but had no effect on cognitive function. However, when the exposure time was 6 h, impaired spatial learning and memory were linked to reduced BDNF, Ac-H3, and Ac-H4, which could be reversed by EE.
Assuntos
Animais , Feminino , Gravidez , Ratos , Disfunção Cognitiva , Acetilação , Histonas , Aprendizagem em Labirinto , Fator Neurotrófico Derivado do Encéfalo , Sevoflurano , HipocampoRESUMO
The use of ulinastatin for pancreatitis and sepsis have been described. This study was designed to evaluate the effect of ulinastatin on vascular endothelial cell damage and coagulation in pregnant women with severe pre-eclampsia (PE).From October 2015 to November 2017 at Tianjin Central Hospital of gynecology and obstetrics in China. Eighty pregnant women with severe PE, who elected to deliver by cesarean section, were randomly assigned to a control group or an ulinastatin group. The plasma concentration of von Willebrand factor (vWF) and platelet granule membrane protein (GMP-140), platelet count, fibrinogen levels, prothrombin time (PT), and partial prothrombin activation time (APTT) were recorded before combined spinal-epidural anesthesia and 40 min after administration in both groups.Ulinastatin attenuates vascular endothelial cell damage in pregnant women with PE as indicated by decreased plasma concentrations of vWF and prolonged APTT.
Assuntos
Células Endoteliais/efeitos dos fármacos , Glicoproteínas/farmacologia , Pré-Eclâmpsia/tratamento farmacológico , Inibidores da Tripsina/farmacologia , Adulto , Coagulação Sanguínea/efeitos dos fármacos , Cesárea/efeitos adversos , Feminino , Fibrinogênio/análise , Glicoproteínas/uso terapêutico , Humanos , Selectina-P/sangue , Contagem de Plaquetas , Pré-Eclâmpsia/sangue , Gravidez , Tempo de Protrombina , Valores de Referência , Reprodutibilidade dos Testes , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento , Inibidores da Tripsina/uso terapêutico , Adulto Jovem , Fator de von Willebrand/análiseRESUMO
Dynamin-related proteins (DRPs) are large multidomain GTPases required for diverse membrane-remodeling events. DRPs self-assemble into helical structures, but how these structures are tailored to their cellular targets remains unclear. We demonstrate that the fungal DRP Vps1 primarily localizes to and functions at the endosomal compartment. We present crystal structures of a Vps1 GTPase-bundle signaling element (BSE) fusion in different nucleotide states to capture GTP hydrolysis intermediates and concomitant conformational changes. Using cryoEM, we determined the structure of full-length GMPPCP-bound Vps1. The Vps1 helix is more open and flexible than that of dynamin. This is due to further opening of the BSEs away from the GTPase domains. A novel interface between adjacent GTPase domains forms in Vps1 instead of the contacts between the BSE and adjacent stalks and GTPase domains as seen in dynamin. Disruption of this interface abolishes Vps1 function in vivo. Hence, Vps1 exhibits a unique helical architecture, highlighting structural flexibilities of DRP self-assembly.