In this review,we summarize the involvement of vitamin C in mental disorders by presenting available evidence on its pharmacological effects in animal models as well as in clinical studies.Vitamin C,especially its red...In this review,we summarize the involvement of vitamin C in mental disorders by presenting available evidence on its pharmacological effects in animal models as well as in clinical studies.Vitamin C,especially its reduced form,has gained interest for its multiple functions in various tissues and organs,including central nervous system(CNS).Vitamin C protects the neuron against oxidative stress,alleviates inflammation,regulates the neurotransmission,affects neuronal development and controls epigenetic function.All of these processes are closely associated with psychopathology.In the past few decades,scientists have revealed that the deficiency of vitamin C may lead to motor deficit,cognitive impairment and aberrant behaviors,whereas supplement of vitamin C has a potential preventive and therapeutic effect on mental illness,such as major depressive disorder(MDD),schizophrenia,anxiety and Alzheimer's disease(AD).Although several studies support a possible role of vitamin C against mental disorders,more researches are essential to accelerate the knowledge and investigate the mechanism in this field.展开更多
Dimethyl sulfide(DMS)has been historically recognized as a metabolite of the marine microorganism or a disgusting component for the smell of halitosis patients.In our recent study,DMS has been identified as a cytoprot...Dimethyl sulfide(DMS)has been historically recognized as a metabolite of the marine microorganism or a disgusting component for the smell of halitosis patients.In our recent study,DMS has been identified as a cytoprotectant that protects against oxidative-stress induced cell death and aging.We found that at near-physiological concentrations,DMS reduced reactive oxygen species(ROS)in cultured PC12 cells and alleviated oxidative stress.The radical-scavenging capacity of DMS at near-physiological concentration was equivalent to endogenous methionine(Met)-centered antioxidant defense.Methionine sulfoxidereductase A(MsrA),the key antioxidant enzyme in Met-centered defense,bound to DMS and promoted its antioxidant capacity via facilitating the reaction of DMS with ROS through a sulfonium intermediate at residues Cys72,Tyr103,Glu115,followed by the release of dimethyl sulfoxide(DMSO).MTT assay and trypan blue test indicated that supplement of DMS exhibited cytoprotection against 6-hydroxydopamine and MPP+induced cell apoptosis.Furthermore,Msr A knockdown abolished the cytoprotective effect of DMS at near-physiological concentrations.The present study reveals new insight into the potential therapeutic value of DMS in Parkinson disease.展开更多
Redox-altered plasticity refers to redox-dependent reversible changes in synaptic plasticity via altering functions of key proteins, such as N-methyl-D-aspartate receptor(NMDAR). Age-related cognitive disorders includ...Redox-altered plasticity refers to redox-dependent reversible changes in synaptic plasticity via altering functions of key proteins, such as N-methyl-D-aspartate receptor(NMDAR). Age-related cognitive disorders includes Alzheimer’s disease(AD), vascular dementia(VD), and age-associated memory impairment(AAMI). Based on the critical role of NMDAR-dependent long-term potentiation(LTP) in memory, the increase of reactive oxygen species in cognitive disorders, and the sensitivity of NMDAR to the redox status, converging lines have suggested the redox-altered NMDAR-dependent plasticity might underlie the synaptic dysfunctions associated with cognitive disorders. In this review, we summarize the involvement of redox-altered plasticity in cognitive disorders by presenting the available evidence. According to reports from our laboratory and other groups, this "redox-altered plasticity" is Hydrogen sulfidemore similar to functional changes rather than organic injuries, and strategies targeting redox-altered plasticity using pharmacological agents might reverse synaptic dysfunctions and memory abnormalities in the early stage of cognitive disorders. Targeting redox modifications for NMDARs may serve as a novel therapeutic strategy for memory deficits.展开更多
Microglia are the major immune cells in the central nervous system and play a key role in the normal function of the brain.Microglia exhibit functional diversity,and they control the inflammation in central nervous sy...Microglia are the major immune cells in the central nervous system and play a key role in the normal function of the brain.Microglia exhibit functional diversity,and they control the inflammation in central nervous system through releasing inflammatory cytokine,clearing apoptotic cells via phagocytosis,regulating synaptic plasticity and the formation of neural network by synapse pruning.Recent studies have strongly indicated that the microglial dysfunction is associated with a variety of neuropsychiatric diseases such as depression,which have been termed as“microgliopathy”.The emergency of advanced technologies and tools has enabled us to comprehensively understand the role of microglia in physiology and pathology,and growing studies have targetted microglia to explore the treatment of neuropsychiatric diseases.Here,we describe the key progress of microglia research,and review the recent developments in the understanding of the role of microglia in physiology and etiology of depression.展开更多
Glutamate acting on AMPA-type ionotropic glutamate receptor(AMPAR) mediates the majority of fast excitatory synaptic transmission in the mammalian central nervous system. Dynamic regulation of AMPAR by post-translatio...Glutamate acting on AMPA-type ionotropic glutamate receptor(AMPAR) mediates the majority of fast excitatory synaptic transmission in the mammalian central nervous system. Dynamic regulation of AMPAR by post-translational modifications is one of the key elements that allow the nervous system to adapt to environment stimulations. S-palmitoylation, an important lipid modification by post-translational addition of a long-chain fatty acid to a cysteine residue, regulates AMPA receptor trafficking, which dynamically affects multiple fundamental brain functions, such as learning and memory. In vivo, S-palmitoylation is controlled by palmitoyl acyl transferases and palmitoyl thioesterases.In this review, we highlight advances in the mechanisms for dynamic AMPA receptors palmitoylation,and discuss how palmitoylation affects AMPA receptors function at synapses in recent years.Pharmacological regulation of S-palmitoylation may serve as a novel therapeutic strategy for neurobiological diseases.展开更多
基金supported by grants from the Foundation for Innovative Research Groups of NSFC(No.81721005)National Natural Science Foundation of China(No.81773712,and No.81473198)+1 种基金the National Basic Research Program of China(973 Program,No.2014CB744601)Program for Changjiang Scholars and Innovative Research Team in University(PCSIRT No.13016)
文摘In this review,we summarize the involvement of vitamin C in mental disorders by presenting available evidence on its pharmacological effects in animal models as well as in clinical studies.Vitamin C,especially its reduced form,has gained interest for its multiple functions in various tissues and organs,including central nervous system(CNS).Vitamin C protects the neuron against oxidative stress,alleviates inflammation,regulates the neurotransmission,affects neuronal development and controls epigenetic function.All of these processes are closely associated with psychopathology.In the past few decades,scientists have revealed that the deficiency of vitamin C may lead to motor deficit,cognitive impairment and aberrant behaviors,whereas supplement of vitamin C has a potential preventive and therapeutic effect on mental illness,such as major depressive disorder(MDD),schizophrenia,anxiety and Alzheimer's disease(AD).Although several studies support a possible role of vitamin C against mental disorders,more researches are essential to accelerate the knowledge and investigate the mechanism in this field.
文摘Dimethyl sulfide(DMS)has been historically recognized as a metabolite of the marine microorganism or a disgusting component for the smell of halitosis patients.In our recent study,DMS has been identified as a cytoprotectant that protects against oxidative-stress induced cell death and aging.We found that at near-physiological concentrations,DMS reduced reactive oxygen species(ROS)in cultured PC12 cells and alleviated oxidative stress.The radical-scavenging capacity of DMS at near-physiological concentration was equivalent to endogenous methionine(Met)-centered antioxidant defense.Methionine sulfoxidereductase A(MsrA),the key antioxidant enzyme in Met-centered defense,bound to DMS and promoted its antioxidant capacity via facilitating the reaction of DMS with ROS through a sulfonium intermediate at residues Cys72,Tyr103,Glu115,followed by the release of dimethyl sulfoxide(DMSO).MTT assay and trypan blue test indicated that supplement of DMS exhibited cytoprotection against 6-hydroxydopamine and MPP+induced cell apoptosis.Furthermore,Msr A knockdown abolished the cytoprotective effect of DMS at near-physiological concentrations.The present study reveals new insight into the potential therapeutic value of DMS in Parkinson disease.
基金supported by grants from the National Natural Science Foundation of China (No. 81773712 to Pengfei WuNos.81471377 and 81671438 to Fang Wang+1 种基金Nos. 81473198 and81673414 to Jianguo Chen)Foundation for Innovative Research Groups of NSFC (No. 81721005 to Jianguo Chen and Fang Wang, China)。
文摘Redox-altered plasticity refers to redox-dependent reversible changes in synaptic plasticity via altering functions of key proteins, such as N-methyl-D-aspartate receptor(NMDAR). Age-related cognitive disorders includes Alzheimer’s disease(AD), vascular dementia(VD), and age-associated memory impairment(AAMI). Based on the critical role of NMDAR-dependent long-term potentiation(LTP) in memory, the increase of reactive oxygen species in cognitive disorders, and the sensitivity of NMDAR to the redox status, converging lines have suggested the redox-altered NMDAR-dependent plasticity might underlie the synaptic dysfunctions associated with cognitive disorders. In this review, we summarize the involvement of redox-altered plasticity in cognitive disorders by presenting the available evidence. According to reports from our laboratory and other groups, this "redox-altered plasticity" is Hydrogen sulfidemore similar to functional changes rather than organic injuries, and strategies targeting redox-altered plasticity using pharmacological agents might reverse synaptic dysfunctions and memory abnormalities in the early stage of cognitive disorders. Targeting redox modifications for NMDARs may serve as a novel therapeutic strategy for memory deficits.
基金This project was supported by the Foundation for Innovative Research Groups of NSFC(No.81721005).
文摘Microglia are the major immune cells in the central nervous system and play a key role in the normal function of the brain.Microglia exhibit functional diversity,and they control the inflammation in central nervous system through releasing inflammatory cytokine,clearing apoptotic cells via phagocytosis,regulating synaptic plasticity and the formation of neural network by synapse pruning.Recent studies have strongly indicated that the microglial dysfunction is associated with a variety of neuropsychiatric diseases such as depression,which have been termed as“microgliopathy”.The emergency of advanced technologies and tools has enabled us to comprehensively understand the role of microglia in physiology and pathology,and growing studies have targetted microglia to explore the treatment of neuropsychiatric diseases.Here,we describe the key progress of microglia research,and review the recent developments in the understanding of the role of microglia in physiology and etiology of depression.
基金supported by grants from the National Basic Research Program of China (the 973 Program, No. 2013CB531303 to Dr. Jianguo Chen No. 2014CB744601 to Fang Wang)+3 种基金the National Natural Scientific Foundation of China (NSFC, No. 81222048 to Fang Wang No. 81302754 to Peng Fei Wu)supported by the International Science & Technology Cooperation Program of China (No. 2011DFA32670 to Jianguo Chen)PCSIRT (No. IRT13016)
文摘Glutamate acting on AMPA-type ionotropic glutamate receptor(AMPAR) mediates the majority of fast excitatory synaptic transmission in the mammalian central nervous system. Dynamic regulation of AMPAR by post-translational modifications is one of the key elements that allow the nervous system to adapt to environment stimulations. S-palmitoylation, an important lipid modification by post-translational addition of a long-chain fatty acid to a cysteine residue, regulates AMPA receptor trafficking, which dynamically affects multiple fundamental brain functions, such as learning and memory. In vivo, S-palmitoylation is controlled by palmitoyl acyl transferases and palmitoyl thioesterases.In this review, we highlight advances in the mechanisms for dynamic AMPA receptors palmitoylation,and discuss how palmitoylation affects AMPA receptors function at synapses in recent years.Pharmacological regulation of S-palmitoylation may serve as a novel therapeutic strategy for neurobiological diseases.