Autistic spectrum disorder(ASD)is a male-biased,heterogeneous neurodevelopmental disorder that affects approximately 1%e2%of the population.Prenatal exposure to valproic acid(VPA)is a recognized risk factor for ASD,bu...Autistic spectrum disorder(ASD)is a male-biased,heterogeneous neurodevelopmental disorder that affects approximately 1%e2%of the population.Prenatal exposure to valproic acid(VPA)is a recognized risk factor for ASD,but the cellular and molecular basis of VPA-induced ASD at the single-cell resolution is unclear.Here,we aim to compare the cellular and molecular differences in the hippocampus between male and female prenatal mice with ASD at the single-cell transcriptomic level.The transcriptomes of more than 45,000 cells are assigned to 12 major cell types,including neurons,glial cells,vascular cells,and immune cells.Cell type-specific genes with altered expression after prenatal VPA exposure are analyzed,and the largest number of differentially expressed genes(DEGs)are found in neurons,choroid plexus epithelial cells,and microglia.In microglia,several pathways related to inflammation are found in both males and females,including the tumor necrosis factor(TNF),nuclear factor kappa B(NF-kB),toll-like receptor(TLR),and mitogen-activated protein kinase(MAPK)signaling pathways,which are important for the induction of autistic-like behavior.Additionally,we note that several X-linked genes,including Bex1,Bex3,and Gria3,were among the male-specific DEGs of neurons.This pioneering study describes the landscape of the transcriptome in the hippocampus of autistic mice.The elucidation of sexual differences could provide innovative strategies for the prevention and treatment of ASD.展开更多
Echinacoside (ECH) is protective in a mouse model of Parkinson' s disease (PD) induced by 1-methyl-4- phenylpyridinium ion (MPP+). To investigate the mechanisms involved, SH-SYSY neuroblastoma ceils were treat...Echinacoside (ECH) is protective in a mouse model of Parkinson' s disease (PD) induced by 1-methyl-4- phenylpyridinium ion (MPP+). To investigate the mechanisms involved, SH-SYSY neuroblastoma ceils were treated with MPP+ or a combination of MPP+ and ECH, and the expression of ATF3 (activating transcription factor 3), CHOP (C/EBP-homologous protein), SCNA (synuclein alpha), and GDNF (glial cell line-derived neurotrophic factor) was assessed. The results showed that ECH significantly improved cell survival by inhibiting the generation of MPP+-induced reactive oxygen species (ROS). In addition, ECH suppressed the ROS and MPP+- induced expression of apoptotic genes (ATF3, CHOP, and SCNA). ECH markedly decreased the MPP+-induced cas- pase-3 activity in a dose-dependent manner. ATF3- knockdown also decreased the CHOP and cleaved caspase- 3 levels and inhibited the apoptosis induced by MPP+. Interestingly, ECH partially restored the GDNF expression that was down-regulated by MPP+. ECH also improved dopaminergic neuron survival during MPP+ treatment and protected these neurons against the apoptosis induced by MPTP. Taken together, these data suggest that the ROS/ ATF3/CHOP pathway plays a critical role in mechanisms by which ECH protects against MPP+-induced apoptosis in PD.展开更多
基金supported by the National Natural Science Foundation of China(82074162 and 82274344)Project for Capacity Promotion of Putuo District Clinical Special Disease“Stroke”,Science and Technology Innovation Project of Putuo District Health System(ptkwws201902 and ptkwws202301)+2 种基金Training Plan of“100 professionals”of Shanghai Putuo District Central Hospital(2022-RCJC-05)Project of“XingLin Scholars Training”of Chengdu University of Traditional Chinese Medicine(YYZX2022170)Shanghai Putuo District Health System Clinical Characteristic Special Disease Construction Project(2023tszb04).
文摘Autistic spectrum disorder(ASD)is a male-biased,heterogeneous neurodevelopmental disorder that affects approximately 1%e2%of the population.Prenatal exposure to valproic acid(VPA)is a recognized risk factor for ASD,but the cellular and molecular basis of VPA-induced ASD at the single-cell resolution is unclear.Here,we aim to compare the cellular and molecular differences in the hippocampus between male and female prenatal mice with ASD at the single-cell transcriptomic level.The transcriptomes of more than 45,000 cells are assigned to 12 major cell types,including neurons,glial cells,vascular cells,and immune cells.Cell type-specific genes with altered expression after prenatal VPA exposure are analyzed,and the largest number of differentially expressed genes(DEGs)are found in neurons,choroid plexus epithelial cells,and microglia.In microglia,several pathways related to inflammation are found in both males and females,including the tumor necrosis factor(TNF),nuclear factor kappa B(NF-kB),toll-like receptor(TLR),and mitogen-activated protein kinase(MAPK)signaling pathways,which are important for the induction of autistic-like behavior.Additionally,we note that several X-linked genes,including Bex1,Bex3,and Gria3,were among the male-specific DEGs of neurons.This pioneering study describes the landscape of the transcriptome in the hippocampus of autistic mice.The elucidation of sexual differences could provide innovative strategies for the prevention and treatment of ASD.
基金supported by the National Natural Science Foundation of China(81202814)the Shanghai Municipal Commission of Health and Family Planning(20124y116)the Young Teachers Training Funding Scheme of Shanghai Colleges and Universities,China(zzszy12026)
文摘Echinacoside (ECH) is protective in a mouse model of Parkinson' s disease (PD) induced by 1-methyl-4- phenylpyridinium ion (MPP+). To investigate the mechanisms involved, SH-SYSY neuroblastoma ceils were treated with MPP+ or a combination of MPP+ and ECH, and the expression of ATF3 (activating transcription factor 3), CHOP (C/EBP-homologous protein), SCNA (synuclein alpha), and GDNF (glial cell line-derived neurotrophic factor) was assessed. The results showed that ECH significantly improved cell survival by inhibiting the generation of MPP+-induced reactive oxygen species (ROS). In addition, ECH suppressed the ROS and MPP+- induced expression of apoptotic genes (ATF3, CHOP, and SCNA). ECH markedly decreased the MPP+-induced cas- pase-3 activity in a dose-dependent manner. ATF3- knockdown also decreased the CHOP and cleaved caspase- 3 levels and inhibited the apoptosis induced by MPP+. Interestingly, ECH partially restored the GDNF expression that was down-regulated by MPP+. ECH also improved dopaminergic neuron survival during MPP+ treatment and protected these neurons against the apoptosis induced by MPTP. Taken together, these data suggest that the ROS/ ATF3/CHOP pathway plays a critical role in mechanisms by which ECH protects against MPP+-induced apoptosis in PD.