Attention is the cornerstone of effective functioning in a complex and information-rich world.While the neural activity of attention has been extensively studied in the cortex,the brain-wide neural activity patterns a...Attention is the cornerstone of effective functioning in a complex and information-rich world.While the neural activity of attention has been extensively studied in the cortex,the brain-wide neural activity patterns are largely unknown.In this study,we conducted a comprehensive analysis of neural activity across the mouse brain during attentional processing using EEG and c-Fos staining,utilizing hierarchical clustering and c-Fos-based functional network analysis to evaluate the c-Fos activation patterns.Our findings reveal that a wide range of brain regions are activated,notably in the high-order cortex,thalamus,and brain stem regions involved in advanced cognition and arousal regulation,with the central lateral nucleus of the thalamus as a strong hub,suggesting the crucial role of the thalamus in attention control.These results provide valuable insights into the neural network mechanisms underlying attention,offering a foundation for formulating functional hypotheses and conducting circuit-level testing.展开更多
Lactate,a byproduct of glycolysis,was thought to be a metabolic waste until the discovery of the Warburg effect.Lactate not only functions as a metabolic substrate to provide energy but can also function as a signalin...Lactate,a byproduct of glycolysis,was thought to be a metabolic waste until the discovery of the Warburg effect.Lactate not only functions as a metabolic substrate to provide energy but can also function as a signaling molecule to modulate cellular functions under pathophysiological conditions.The Astrocyte-Neuron Lactate Shuttle has cla rified that lactate plays a pivotal role in the central nervous system.Moreover,protein lactylation highlights the novel role of lactate in regulating transcription,cellular functions,and disease development.This review summarizes the recent advances in lactate metabolism and its role in neurodegenerative diseases,thus providing optimal pers pectives for future research.展开更多
Microglia-mediated neuroinflammation is widely perceived as a contributor to numerous neurological diseases and mental disorders including depression.Discs large homolog 1(Dlg1),an adaptor protein,regulates cell polar...Microglia-mediated neuroinflammation is widely perceived as a contributor to numerous neurological diseases and mental disorders including depression.Discs large homolog 1(Dlg1),an adaptor protein,regulates cell polarization and the function of K?channels,which are reported to regulate the activation of microglia.However,little is known about the role of Dlg1 in microglia and the maintenance of central nervous system homeostasis.In this study,we found that Dlg1 knockdown suppressed lipopolysaccharide(LPS)-induced inflammation by downregulating the activation of nuclear factor-jB signaling and the mitogen-activated protein kinase pathway in microglia.Moreover,using an inducible Dlg1 microglia-specific knockout(Dlg1flox/flox;CX3CR1CreER)mouse line,we found that microglial Dlg1 knockout reduced the activation of microglia and alleviated the LPS-induced depressionlike behavior.In summary,our results demonstrated that Dlg1 plays a critical role in microglial activation and thus provides a potential therapeutic target for the clinical treatment of depression.展开更多
Astrocytes are an abundant subgroup of cells in the central nervous system(CNS)that play a critical role in controlling neuronal circuits involved in emotion,learning,and memory.In clinical cases,multiple chronic brai...Astrocytes are an abundant subgroup of cells in the central nervous system(CNS)that play a critical role in controlling neuronal circuits involved in emotion,learning,and memory.In clinical cases,multiple chronic brain diseases may cause psychosocial and cognitive impairment,such as depression and Alzheimer’s disease(AD).For years,complex pathological conditions driven by depression and AD have been widely perceived to contribute to a high risk of disability,resulting in gradual loss of self-care ability,lower life qualities,and vast burden on human society.Interestingly,correlational research on depression and AD has shown that depression might be a prodrome of progressive degenerative neurological disease.As a kind of multifunctional glial cell in the CNS,astrocytes maintain physiological function via supporting neuronal cells,modulating pathologic niche,and regulating energy metabolism.Mounting evidence has shown that astrocytic dysfunction is involved in the progression of depression and AD.We herein review the current findings on the roles and mechanisms of astrocytes in the development of depression and AD,with an implication of potential therapeutic avenue for these diseases by targeting astrocytes.展开更多
Dear Editor,Glutamate excitotoxicity due to its accumulation in the extracellular space is a major factor to the brain damage that occurs during the early stages of cerebral ischemia1.GLT-1 is mainly expressed in astr...Dear Editor,Glutamate excitotoxicity due to its accumulation in the extracellular space is a major factor to the brain damage that occurs during the early stages of cerebral ischemia1.GLT-1 is mainly expressed in astrocytes,and it is responsible for almost 90%of glutamate uptake in the brain2.Although GLT-1 upregulation under the administration of ceftriaxone reduces ischemic brain damage,translational application of ceftriaxone in acute ischemia treatment is limited because several days are needed for the upregulation of GLT-1^(3),which misses the critical time window during which suppression of excitotoxicity will be effective.展开更多
Transcription factors(TFs)control an array of expressed genes.However,the specifics of how a gene is expressed in time and space as controlled by a TF remain largely unknown.Here,in TRPC6-regulated proline oxidase 1(P...Transcription factors(TFs)control an array of expressed genes.However,the specifics of how a gene is expressed in time and space as controlled by a TF remain largely unknown.Here,in TRPC6-regulated proline oxidase 1(POX)transcription in human glioma,we report that OIP5-AS1,a long noncoding RNA,determines the specificity of p53-driven POX expression.The OIP5-AS1/p53 complex via its 24 nucleotides binds to the POX promoter and is necessary for POX expression but not for p21 transcription.An O-site in the POX promoter to which OIP5-AS1 binds was identified that is required for OIP5-AS1/p53 binding and POX transcription.Blocking OIP5-AS1 binding to the O-site inhibits POX transcription and promotes glioma development.Thus,the OIP5-AS1/O-site module decides p53-controlled POX expression as regulated by TRPC6 and affects glioma development.展开更多
文摘Attention is the cornerstone of effective functioning in a complex and information-rich world.While the neural activity of attention has been extensively studied in the cortex,the brain-wide neural activity patterns are largely unknown.In this study,we conducted a comprehensive analysis of neural activity across the mouse brain during attentional processing using EEG and c-Fos staining,utilizing hierarchical clustering and c-Fos-based functional network analysis to evaluate the c-Fos activation patterns.Our findings reveal that a wide range of brain regions are activated,notably in the high-order cortex,thalamus,and brain stem regions involved in advanced cognition and arousal regulation,with the central lateral nucleus of the thalamus as a strong hub,suggesting the crucial role of the thalamus in attention control.These results provide valuable insights into the neural network mechanisms underlying attention,offering a foundation for formulating functional hypotheses and conducting circuit-level testing.
基金supported by the National Natural Science Foundation of China,Nos.82230042 and 81930029(to ZY),U2004201(to FG and RYP)the China Postdoctoral Science Foundation,No.2020M683748(to RYP)。
文摘Lactate,a byproduct of glycolysis,was thought to be a metabolic waste until the discovery of the Warburg effect.Lactate not only functions as a metabolic substrate to provide energy but can also function as a signaling molecule to modulate cellular functions under pathophysiological conditions.The Astrocyte-Neuron Lactate Shuttle has cla rified that lactate plays a pivotal role in the central nervous system.Moreover,protein lactylation highlights the novel role of lactate in regulating transcription,cellular functions,and disease development.This review summarizes the recent advances in lactate metabolism and its role in neurodegenerative diseases,thus providing optimal pers pectives for future research.
基金the National Natural Science Foundation of China(82071218,81630026,and 81930029).
文摘Microglia-mediated neuroinflammation is widely perceived as a contributor to numerous neurological diseases and mental disorders including depression.Discs large homolog 1(Dlg1),an adaptor protein,regulates cell polarization and the function of K?channels,which are reported to regulate the activation of microglia.However,little is known about the role of Dlg1 in microglia and the maintenance of central nervous system homeostasis.In this study,we found that Dlg1 knockdown suppressed lipopolysaccharide(LPS)-induced inflammation by downregulating the activation of nuclear factor-jB signaling and the mitogen-activated protein kinase pathway in microglia.Moreover,using an inducible Dlg1 microglia-specific knockout(Dlg1flox/flox;CX3CR1CreER)mouse line,we found that microglial Dlg1 knockout reduced the activation of microglia and alleviated the LPS-induced depressionlike behavior.In summary,our results demonstrated that Dlg1 plays a critical role in microglial activation and thus provides a potential therapeutic target for the clinical treatment of depression.
基金We sincerely thank the National Natural Science Foundation of China(Nos.81930029,81630026,and 81501200)the Beijing Nature Science Foundation(No.7161009).
文摘Astrocytes are an abundant subgroup of cells in the central nervous system(CNS)that play a critical role in controlling neuronal circuits involved in emotion,learning,and memory.In clinical cases,multiple chronic brain diseases may cause psychosocial and cognitive impairment,such as depression and Alzheimer’s disease(AD).For years,complex pathological conditions driven by depression and AD have been widely perceived to contribute to a high risk of disability,resulting in gradual loss of self-care ability,lower life qualities,and vast burden on human society.Interestingly,correlational research on depression and AD has shown that depression might be a prodrome of progressive degenerative neurological disease.As a kind of multifunctional glial cell in the CNS,astrocytes maintain physiological function via supporting neuronal cells,modulating pathologic niche,and regulating energy metabolism.Mounting evidence has shown that astrocytic dysfunction is involved in the progression of depression and AD.We herein review the current findings on the roles and mechanisms of astrocytes in the development of depression and AD,with an implication of potential therapeutic avenue for these diseases by targeting astrocytes.
基金the National Natural Science Foundation of China(81830034)Shenzhen-Hong Kong Institute of Brain ScienceShenzhen Fundamental Research Institutions(2021SHIBS0002)Shenzhen Science and Technology Innovation Committee Research Grants(JCYJ20180504165806229,KQJSCX20180322151111754 to S.T.H.).
文摘Dear Editor,Glutamate excitotoxicity due to its accumulation in the extracellular space is a major factor to the brain damage that occurs during the early stages of cerebral ischemia1.GLT-1 is mainly expressed in astrocytes,and it is responsible for almost 90%of glutamate uptake in the brain2.Although GLT-1 upregulation under the administration of ceftriaxone reduces ischemic brain damage,translational application of ceftriaxone in acute ischemia treatment is limited because several days are needed for the upregulation of GLT-1^(3),which misses the critical time window during which suppression of excitotoxicity will be effective.
基金This work was partially supported by the grant(81830043)from the National Natural Science Foundation of China(NSFC).
文摘Transcription factors(TFs)control an array of expressed genes.However,the specifics of how a gene is expressed in time and space as controlled by a TF remain largely unknown.Here,in TRPC6-regulated proline oxidase 1(POX)transcription in human glioma,we report that OIP5-AS1,a long noncoding RNA,determines the specificity of p53-driven POX expression.The OIP5-AS1/p53 complex via its 24 nucleotides binds to the POX promoter and is necessary for POX expression but not for p21 transcription.An O-site in the POX promoter to which OIP5-AS1 binds was identified that is required for OIP5-AS1/p53 binding and POX transcription.Blocking OIP5-AS1 binding to the O-site inhibits POX transcription and promotes glioma development.Thus,the OIP5-AS1/O-site module decides p53-controlled POX expression as regulated by TRPC6 and affects glioma development.
