Oligodendrocyte precursor cells(OPCs)tile the central nervous system ubiquitously,accounting for about 5%of the total cell population in the central nervous system.Beyond their role in myelination,OPCs actively shape ...Oligodendrocyte precursor cells(OPCs)tile the central nervous system ubiquitously,accounting for about 5%of the total cell population in the central nervous system.Beyond their role in myelination,OPCs actively shape neural circuits(Fang and Bai,2023),by releasing neuromodulators,pruning synapses,maintaining the homeostasis of extracellular potassium concentration,and interacting with endothelial cells.展开更多
Oxidative stress influences cell survival and homeostasis,but the mechanisms underlying the biological effects of oxidative stress remain to be elucidated.We have defined that the protein kinase MST1 mediates oxidativ...Oxidative stress influences cell survival and homeostasis,but the mechanisms underlying the biological effects of oxidative stress remain to be elucidated.We have defined that the protein kinase MST1 mediates oxidative stress-induced cell death in primary mammalian neurons by directly activating the FOXO transcription factors.However,the upstream regulator of MST1 is largely unknown.Here,we demonstarte the c-Abl-MST1-FOXO signaling cascade mediates oxidative stress-induced neuronal cell death.C-Abl phosphorylates MST1 at a conserve site,Tyrosine 433,that leads to stabilization and activation of MST1.展开更多
Tiantai No.1, a Chinese medicine predominantly composed of powdered Rhizoma Gastrodiae, Radix Ginseng, and Ginkgo leaf at a ratio of 2：1：2 and dissolved in pure water, is neuroprotective in animal models of various ...Tiantai No.1, a Chinese medicine predominantly composed of powdered Rhizoma Gastrodiae, Radix Ginseng, and Ginkgo leaf at a ratio of 2：1：2 and dissolved in pure water, is neuroprotective in animal models of various cognitive disorders, but its molecular mechanism remains unclear. We administered Tiantai No.1 intragastrically to senescence-accelerated mouse prone 8（SAMP8） mice（a model of Alzheimer＇s disease） at doses of 50, 100 or 150 mg/kg per day for 8 weeks and evaluated their behavior in the Morris water maze and expression of Alzheimer＇s disease-related proteins in the brain. Tiantai No.1 shortened the escape latency in the water maze training trials, and increased swimming time in the target quadrant during the spatial probe test, indicating that Tiantai No.1 improved learning and memory in SAMP8 mice. Immunohistochemistry revealed that Tiantai No.1 restored the proliferation potential of Ki67-positive cells in the hippocampus. In addition, mice that had received Tiantai No.1 had fewer astrocytes, and less accumulation of amyloid-beta and phosphorylated tau. These results suggest that Tiantai No.1 is neuroprotective in the SAMP8 mouse model of Alzheimer＇s disease and acts by restoring neuronal number and proliferation potential in the hippocampus, decreasing astrocyte infiltration, and reducing the accumulation of amyloid-beta and phosphorylated tau.展开更多
The secondary motor cortex(M2)encodes choice-related information and plays an important role in cue-guided actions.M2 neurons innervate the dorsal striatum(DS),which also contributes to decision-making behavior,yet ho...The secondary motor cortex(M2)encodes choice-related information and plays an important role in cue-guided actions.M2 neurons innervate the dorsal striatum(DS),which also contributes to decision-making behavior,yet how M2 modulates signals in the DS to influence perceptual decision-making is unclear.Using mice performing a visual Go/No-Go task,we showed that inactivating M2 projections to the DS impaired performance by increasing the false alarm(FA)rate to the reward-irrelevant No-Go stimulus.The choice signal of M2 neurons correlated with behavioral performance,and the inactivation of M2 neurons projecting to the DS reduced the choice signal in the DS.By measuring and manipulating the responses of direct or indirect pathway striatal neurons defined by M2 inputs,we found that the indirect pathway neurons exhibited a shorter response latency to the No-Go stimulus,and inactivating their early responses increased the FA rate.These results demonstrate that the M2-to-DS pathway is crucial for suppressing inappropriate responses in perceptual decision behavior.展开更多
基金supported by DeutscheForschungsgemeinschaft(BA 8014/1-1 to XB)University of Saarland(NanoBioMed Young Investigatorgrant 2021 to XB,Anschubsfinanzierung2024to XB,HOMFORExzellenz2025 andAnschubsfinanzierung2025 to LPF)the ChinaPharmaceutical University(UndergraduateInternship Program to YZ).
文摘Oligodendrocyte precursor cells(OPCs)tile the central nervous system ubiquitously,accounting for about 5%of the total cell population in the central nervous system.Beyond their role in myelination,OPCs actively shape neural circuits(Fang and Bai,2023),by releasing neuromodulators,pruning synapses,maintaining the homeostasis of extracellular potassium concentration,and interacting with endothelial cells.
文摘Oxidative stress influences cell survival and homeostasis,but the mechanisms underlying the biological effects of oxidative stress remain to be elucidated.We have defined that the protein kinase MST1 mediates oxidative stress-induced cell death in primary mammalian neurons by directly activating the FOXO transcription factors.However,the upstream regulator of MST1 is largely unknown.Here,we demonstarte the c-Abl-MST1-FOXO signaling cascade mediates oxidative stress-induced neuronal cell death.C-Abl phosphorylates MST1 at a conserve site,Tyrosine 433,that leads to stabilization and activation of MST1.
基金funded by the National Natural Science Foundation of China,No.81473742the Guangdong Science and Technology Foundation,No.2013B021800101the Shenzhen Major Project of Science and Technology Planning,No.JCYJ20130401115231337
文摘Tiantai No.1, a Chinese medicine predominantly composed of powdered Rhizoma Gastrodiae, Radix Ginseng, and Ginkgo leaf at a ratio of 2：1：2 and dissolved in pure water, is neuroprotective in animal models of various cognitive disorders, but its molecular mechanism remains unclear. We administered Tiantai No.1 intragastrically to senescence-accelerated mouse prone 8（SAMP8） mice（a model of Alzheimer＇s disease） at doses of 50, 100 or 150 mg/kg per day for 8 weeks and evaluated their behavior in the Morris water maze and expression of Alzheimer＇s disease-related proteins in the brain. Tiantai No.1 shortened the escape latency in the water maze training trials, and increased swimming time in the target quadrant during the spatial probe test, indicating that Tiantai No.1 improved learning and memory in SAMP8 mice. Immunohistochemistry revealed that Tiantai No.1 restored the proliferation potential of Ki67-positive cells in the hippocampus. In addition, mice that had received Tiantai No.1 had fewer astrocytes, and less accumulation of amyloid-beta and phosphorylated tau. These results suggest that Tiantai No.1 is neuroprotective in the SAMP8 mouse model of Alzheimer＇s disease and acts by restoring neuronal number and proliferation potential in the hippocampus, decreasing astrocyte infiltration, and reducing the accumulation of amyloid-beta and phosphorylated tau.
基金This work was supported by the STI2030-Major Projects(2021ZD0203700/2021ZD0203703)the National Natural Science Foundation of China(31771151,32171030,and 32100829),the Lingang Lab(LG202104-01-03)+1 种基金Shanghai Municipal Science and Technology Major Project(2018SHZDZX05)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB32010200).
文摘The secondary motor cortex(M2)encodes choice-related information and plays an important role in cue-guided actions.M2 neurons innervate the dorsal striatum(DS),which also contributes to decision-making behavior,yet how M2 modulates signals in the DS to influence perceptual decision-making is unclear.Using mice performing a visual Go/No-Go task,we showed that inactivating M2 projections to the DS impaired performance by increasing the false alarm(FA)rate to the reward-irrelevant No-Go stimulus.The choice signal of M2 neurons correlated with behavioral performance,and the inactivation of M2 neurons projecting to the DS reduced the choice signal in the DS.By measuring and manipulating the responses of direct or indirect pathway striatal neurons defined by M2 inputs,we found that the indirect pathway neurons exhibited a shorter response latency to the No-Go stimulus,and inactivating their early responses increased the FA rate.These results demonstrate that the M2-to-DS pathway is crucial for suppressing inappropriate responses in perceptual decision behavior.
