Clinical researches including the Mayo Anesthesia Safety in Kids (MASK) study have found that children undergoing multiple anesthesia may have a higher risk of fne motor control difculties. However, the underlying mec...Clinical researches including the Mayo Anesthesia Safety in Kids (MASK) study have found that children undergoing multiple anesthesia may have a higher risk of fne motor control difculties. However, the underlying mechanisms remain elusive. Here, we report that erythropoietin receptor (EPOR), a microglial receptor associated with phagocytic activity, was signifcantly downregulated in the medial prefrontal cortex of young mice after multiple sevofurane anesthesia exposure. Importantly, we found that the inhibited erythropoietin (EPO)/EPOR signaling axis led to microglial polarization, excessive excitatory synaptic pruning, and abnormal fne motor control skills in mice with multiple anesthesia exposure, and those above-mentioned situations were fully reversed by supplementing EPO-derived peptide ARA290 by intraperitoneal injection. Together, the microglial EPOR was identifed as a key mediator regulating early synaptic development in this study, which impacted sevoflurane-induced fine motor dysfunction. Moreover, ARA290 might serve as a new treatment against neurotoxicity induced by general anesthesia in clinical practice by targeting the EPO/EPOR signaling pathway.展开更多
Chitosan oligosaccharides(COSs)have been reported to possess a broad range of activities such as antitumor,antioxidant and neuroprotective activities.In this study,the protective efects and mechanisms of peracetylated...Chitosan oligosaccharides(COSs)have been reported to possess a broad range of activities such as antitumor,antioxidant and neuroprotective activities.In this study,the protective efects and mechanisms of peracetylated chitosan oligosaccharides(PACOs)against Aβ-induced cognitive defcits were investigated in Sprague–Dawley(SD)rats.PACOs treatment signifcantly improved the learning and memory function of Alzheimer’s disease(AD)rats and attenuated the neuron cell damage caused by Aβ.PACOs also markedly reduced the levels of lactate dehydrogenase(LDH)and Malondialdehyde(MDA)and decreased the phosphorylation of Tau protein to inhibit oxidative injury and infammatory responses in AD rats.Further studies indicated that PACOs may promote the repair of Aβinduced nerve damage and inhibit neuronal apoptosis mainly through regulating PI3K/Akt/GSK3βsignaling pathway.Consistently,the transcriptome analysis verifed that the diferentially expressed genes(DEGs)were mainly involved in neuron development and the PI3K-Akt signaling pathway.Taken together,peracetylated chitosan oligosaccharides(PACOs)have the potential to be developed into novel anti-AD agents targeting the cellular PI3K/Akt/GSK3βsignaling pathway.展开更多
The epigenetic clock is defned by the DNA methylation(DNAm)level and has been extensively applied to distinguish biological age from chronological age.Aging-related neurodegeneration is associated with epigenetic alte...The epigenetic clock is defned by the DNA methylation(DNAm)level and has been extensively applied to distinguish biological age from chronological age.Aging-related neurodegeneration is associated with epigenetic alteration,which determines the status of diseases.In recent years,extensive research has shown that physical exercise(PE)can afect the DNAm level,implying a reversal of the epigenetic clock in neurodegeneration.PE also regulates brain plas‑ticity,neuroinfammation,and molecular signaling cascades associated with epigenetics.This review summarizes the efects of PE on neurodegenerative diseases via both general and disease-specifc DNAm mechanisms,and discusses epigenetic modifcations that alleviate the pathological symptoms of these diseases.This may lead to probing of the underpinnings of neurodegenerative disorders and provide valuable therapeutic references for cognitive and motor dysfunction.展开更多
基金supported by grants from the National Natural Science Foundation of China(82101534,82171170,and 82201414)the Natural Science Foundation of Shaanxi Provence(2024JCYBMS659)the Science and Technology Plan in Xi’an of China(23YXYJ0134)。
文摘Clinical researches including the Mayo Anesthesia Safety in Kids (MASK) study have found that children undergoing multiple anesthesia may have a higher risk of fne motor control difculties. However, the underlying mechanisms remain elusive. Here, we report that erythropoietin receptor (EPOR), a microglial receptor associated with phagocytic activity, was signifcantly downregulated in the medial prefrontal cortex of young mice after multiple sevofurane anesthesia exposure. Importantly, we found that the inhibited erythropoietin (EPO)/EPOR signaling axis led to microglial polarization, excessive excitatory synaptic pruning, and abnormal fne motor control skills in mice with multiple anesthesia exposure, and those above-mentioned situations were fully reversed by supplementing EPO-derived peptide ARA290 by intraperitoneal injection. Together, the microglial EPOR was identifed as a key mediator regulating early synaptic development in this study, which impacted sevoflurane-induced fine motor dysfunction. Moreover, ARA290 might serve as a new treatment against neurotoxicity induced by general anesthesia in clinical practice by targeting the EPO/EPOR signaling pathway.
基金This work was supported by National Natural Science Foundation of China(31500646,81874320,and 81672585)Shandong Major Science and Technology Project(2021ZDSYS22)+2 种基金the Promotive Research Fund for Excellent Young and Middle-aged Scientists of Shandong Province(BS2015YY040)Qingdao Science and Technology Development project(15-9-1-67-JCH)Youth Research Fund of Afliated Hospital of Qingdao University(QDFYQN202101003).
文摘Chitosan oligosaccharides(COSs)have been reported to possess a broad range of activities such as antitumor,antioxidant and neuroprotective activities.In this study,the protective efects and mechanisms of peracetylated chitosan oligosaccharides(PACOs)against Aβ-induced cognitive defcits were investigated in Sprague–Dawley(SD)rats.PACOs treatment signifcantly improved the learning and memory function of Alzheimer’s disease(AD)rats and attenuated the neuron cell damage caused by Aβ.PACOs also markedly reduced the levels of lactate dehydrogenase(LDH)and Malondialdehyde(MDA)and decreased the phosphorylation of Tau protein to inhibit oxidative injury and infammatory responses in AD rats.Further studies indicated that PACOs may promote the repair of Aβinduced nerve damage and inhibit neuronal apoptosis mainly through regulating PI3K/Akt/GSK3βsignaling pathway.Consistently,the transcriptome analysis verifed that the diferentially expressed genes(DEGs)were mainly involved in neuron development and the PI3K-Akt signaling pathway.Taken together,peracetylated chitosan oligosaccharides(PACOs)have the potential to be developed into novel anti-AD agents targeting the cellular PI3K/Akt/GSK3βsignaling pathway.
基金This research was supported by the National Natural Science Foundation of China(31671062 and 81870820 to N.-J.X.31900796 to X.-D.L),Shanghai Brain-Intelligence Project from the Science and Technology Commission of Shanghai Municipality(16JC1420500 and 18JC1420302)the Innovative Research Team of High-level Local Universities in Shanghai.
文摘The epigenetic clock is defned by the DNA methylation(DNAm)level and has been extensively applied to distinguish biological age from chronological age.Aging-related neurodegeneration is associated with epigenetic alteration,which determines the status of diseases.In recent years,extensive research has shown that physical exercise(PE)can afect the DNAm level,implying a reversal of the epigenetic clock in neurodegeneration.PE also regulates brain plas‑ticity,neuroinfammation,and molecular signaling cascades associated with epigenetics.This review summarizes the efects of PE on neurodegenerative diseases via both general and disease-specifc DNAm mechanisms,and discusses epigenetic modifcations that alleviate the pathological symptoms of these diseases.This may lead to probing of the underpinnings of neurodegenerative disorders and provide valuable therapeutic references for cognitive and motor dysfunction.
