A rat model of Parkinson＇s disease was established by 6-hydroxydopamine injection into the medial forebrain bundle. Bone marrow-derived mesenchymal stem cells （BMSCs） were isolated from the femur and tibia, and wer...A rat model of Parkinson＇s disease was established by 6-hydroxydopamine injection into the medial forebrain bundle. Bone marrow-derived mesenchymal stem cells （BMSCs） were isolated from the femur and tibia, and were co-cultured with 10% and 60% lesioned or intact striatal extracts. The results showed that when exposed to lesioned striatal extracts, BMSCs developed bipolar or multi-polar morphologies, and there was an increase in the percentage of cells that expressed glial fibrillary acidic protein （GFAP）, nestin and neuron-specific enolase （NSE）. Moreover, the percentage of NSE-positive cells increased with increasing concentrations of lesioned striatal extracts. However, intact striatal extracts only increased the percentage of GFAP-positive cells. The findings suggest that striatal extracts from Parkinson＇s disease rats induce BMSCs to differentiate into neuronal-like cells in vitro.展开更多
Intracerebral hemorrhage （ICH） is a stroke subtype caused by spontaneous rupture of small vessels and bleeding into the brain paren- chyma, resulting in cell death and sensorimotor deficits. Despite the greater prev...Intracerebral hemorrhage （ICH） is a stroke subtype caused by spontaneous rupture of small vessels and bleeding into the brain paren- chyma, resulting in cell death and sensorimotor deficits. Despite the greater prevalence of the ischemic form of stroke （87%）, ICH has the highest mortality rate of all stroke subtypes. The striatum is the most affected structure in hemorrhagic stroke （35-70%）, followed by cere- bral cortex （15-30%）, brain stem and cerebellum （5-10%）; patients suffering striatal and/or cortical ICH bear persistent sensorimotor disabilities. Although chronic sensorimotor impairment is established, a considerable amount of patients experience some degree of spontaneous recovery during the first six months after stroke （Qureshi et al., 2009）, and the neurobiological basis of this process is not understood.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
The dopamine D1-D2 receptor agonist, R-apomorphine, has been shown to be neuroprotective in different models of Parkinson’s disease. Different mechanisms of action for this effect have been proposed, but not verified...The dopamine D1-D2 receptor agonist, R-apomorphine, has been shown to be neuroprotective in different models of Parkinson’s disease. Different mechanisms of action for this effect have been proposed, but not verified in the striatal 6-hydroxydopamine rat model. In this study, the expression of a set of genes involved in 1) signaling, 2) growth and differentiation, 3) neuronal regeneration and survival, 4) apoptosis and 5) inflammation in the striatum was measured after a subchronic R-apomorphine treatment (10 mg/kg/day, subcutaneously, during 11 days) in the striatal 6-hydroxydopamine rat model. The expression of 84 genes was analysed by using the rat neurotrophins and receptors RT2 ProfilerTM PCR array. The neuroprotective effects of R-apomorphine in the striatal 6-hydroxydopamine model were confirmed by neurochemical and behavioural analysis. The expression data suggest the observed neuroprotection involved the alteration of the gene and the protein expression levels of the anti-inflammatory corticotropin releasing hormone receptor (CRHR) 1 and the pro-inflammatory CRHR2 receptor confirming its potential anti-inflammatory action.展开更多
The striatum is the main input structure of the basal ganglia and is involved in voluntary motor control,habit learning and reward processing.Medium spiny neurons（MSNs）comprise80%and 95%of striatal neurons in primat...The striatum is the main input structure of the basal ganglia and is involved in voluntary motor control,habit learning and reward processing.Medium spiny neurons（MSNs）comprise80%and 95%of striatal neurons in primates and rodents,respectively.展开更多
Attention deficit hyperactivity disorder（ADHD）is a common childhood neuropsychiatric disorder that has been linked to the dopaminergic system. This study aimed to investigate the effects of regulation of the dopamin...Attention deficit hyperactivity disorder（ADHD）is a common childhood neuropsychiatric disorder that has been linked to the dopaminergic system. This study aimed to investigate the effects of regulation of the dopamine D4 receptor（DRD4） on functional brain activity during the resting state in ADHD children using the methods of regional homogeneity（Re Ho） and functional connectivity（FC）. Resting-state functional magnetic resonance imaging data were analyzed in 49 children with ADHD. All participants were classified as either carriers of the DRD44-repeat/4-repeat（4 R/4 R） allele（n = 30） or the DRD42-repeat（2 R） allele（n = 19）. The results showed that participants with the DRD4 2 R allele had decreased Re Ho bilaterally in the posterior lobes of the cerebellum, while Re Ho was increased in the left angular gyrus. Compared with participants carrying the DRD4 4 R/4 R allele, those with the DRD4 2 R allele showed decreased FC to the left angular gyrus in the left striatum, right inferior frontal gyrus, and bilateral lobes of the cerebellum. The increased FC regions included the left superior frontal gyrus, medial frontal gyrus, and rectus gyrus. These data suggest that the DRD4 polymorphisms are associated with localized brain activity and specific functional connections, including abnormality in the frontal-striatal-cerebellar loop. Our study not only enhances the understanding of the correlation between the cerebellar lobes and ADHD, but also provides an imaging basis for explaining the neural mechanisms underlying ADHD in children.展开更多
目的:研究纹状体提取液诱导大鼠骨髓间充质干细胞(MSCs)分化为多巴胺能神经元(DN)的可行性。方法:体外培养出MSCs,经流式细胞仪鉴定后分为A、B、C 3组,前5 d每组均用预诱导液诱导,后10 d A组换用1∶1体积比稀释的纹状体提取液,B组换用1...目的:研究纹状体提取液诱导大鼠骨髓间充质干细胞(MSCs)分化为多巴胺能神经元(DN)的可行性。方法:体外培养出MSCs,经流式细胞仪鉴定后分为A、B、C 3组,前5 d每组均用预诱导液诱导,后10 d A组换用1∶1体积比稀释的纹状体提取液,B组换用1∶2体积比稀释的纹状体提取液,C组则续用不含提取液的预诱导液诱导,最后将分化出的细胞用酪氨酸羟化酶(TH)免疫组化鉴定,行阳性细胞计数,确定各组DN阳性率。结果:A、B、C 3组诱导出的DN阳性率分别是11.9%、8.3%及1.6%,A组和C组有显著性差异(P<0.05)。结论:纹状体提取液能诱导MSCs向DN分化。展开更多
文摘A rat model of Parkinson＇s disease was established by 6-hydroxydopamine injection into the medial forebrain bundle. Bone marrow-derived mesenchymal stem cells （BMSCs） were isolated from the femur and tibia, and were co-cultured with 10% and 60% lesioned or intact striatal extracts. The results showed that when exposed to lesioned striatal extracts, BMSCs developed bipolar or multi-polar morphologies, and there was an increase in the percentage of cells that expressed glial fibrillary acidic protein （GFAP）, nestin and neuron-specific enolase （NSE）. Moreover, the percentage of NSE-positive cells increased with increasing concentrations of lesioned striatal extracts. However, intact striatal extracts only increased the percentage of GFAP-positive cells. The findings suggest that striatal extracts from Parkinson＇s disease rats induce BMSCs to differentiate into neuronal-like cells in vitro.
文摘Intracerebral hemorrhage （ICH） is a stroke subtype caused by spontaneous rupture of small vessels and bleeding into the brain paren- chyma, resulting in cell death and sensorimotor deficits. Despite the greater prevalence of the ischemic form of stroke （87%）, ICH has the highest mortality rate of all stroke subtypes. The striatum is the most affected structure in hemorrhagic stroke （35-70%）, followed by cere- bral cortex （15-30%）, brain stem and cerebellum （5-10%）; patients suffering striatal and/or cortical ICH bear persistent sensorimotor disabilities. Although chronic sensorimotor impairment is established, a considerable amount of patients experience some degree of spontaneous recovery during the first six months after stroke （Qureshi et al., 2009）, and the neurobiological basis of this process is not understood.
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.
基金financial support of the Institute for the promotion of Innovation by Science and Technology in Flanders(IWT)(IWT420)National Fund for Scientific Research(FWO-Vlaanderen)(G.0071.05)and of the Research Council of the Vrije Universiteit Brusselresearch grant from the IWT(IWT420).
文摘The dopamine D1-D2 receptor agonist, R-apomorphine, has been shown to be neuroprotective in different models of Parkinson’s disease. Different mechanisms of action for this effect have been proposed, but not verified in the striatal 6-hydroxydopamine rat model. In this study, the expression of a set of genes involved in 1) signaling, 2) growth and differentiation, 3) neuronal regeneration and survival, 4) apoptosis and 5) inflammation in the striatum was measured after a subchronic R-apomorphine treatment (10 mg/kg/day, subcutaneously, during 11 days) in the striatal 6-hydroxydopamine rat model. The expression of 84 genes was analysed by using the rat neurotrophins and receptors RT2 ProfilerTM PCR array. The neuroprotective effects of R-apomorphine in the striatal 6-hydroxydopamine model were confirmed by neurochemical and behavioural analysis. The expression data suggest the observed neuroprotection involved the alteration of the gene and the protein expression levels of the anti-inflammatory corticotropin releasing hormone receptor (CRHR) 1 and the pro-inflammatory CRHR2 receptor confirming its potential anti-inflammatory action.
基金supported by funding from the UK Medical Research Council,EU Framework Programme 7 Neurostemcell and Repair-HDBNA2015 Festival of NeuroscienceINTR12 2013
文摘The striatum is the main input structure of the basal ganglia and is involved in voluntary motor control,habit learning and reward processing.Medium spiny neurons（MSNs）comprise80%and 95%of striatal neurons in primates and rodents,respectively.
基金supported by the Natural Science Foundation of Zhejiang Province, China (No. LY14H180006, LQ18H090009)the Natural Science Foundation of Jiangsu Province (BK20160142)
文摘Attention deficit hyperactivity disorder（ADHD）is a common childhood neuropsychiatric disorder that has been linked to the dopaminergic system. This study aimed to investigate the effects of regulation of the dopamine D4 receptor（DRD4） on functional brain activity during the resting state in ADHD children using the methods of regional homogeneity（Re Ho） and functional connectivity（FC）. Resting-state functional magnetic resonance imaging data were analyzed in 49 children with ADHD. All participants were classified as either carriers of the DRD44-repeat/4-repeat（4 R/4 R） allele（n = 30） or the DRD42-repeat（2 R） allele（n = 19）. The results showed that participants with the DRD4 2 R allele had decreased Re Ho bilaterally in the posterior lobes of the cerebellum, while Re Ho was increased in the left angular gyrus. Compared with participants carrying the DRD4 4 R/4 R allele, those with the DRD4 2 R allele showed decreased FC to the left angular gyrus in the left striatum, right inferior frontal gyrus, and bilateral lobes of the cerebellum. The increased FC regions included the left superior frontal gyrus, medial frontal gyrus, and rectus gyrus. These data suggest that the DRD4 polymorphisms are associated with localized brain activity and specific functional connections, including abnormality in the frontal-striatal-cerebellar loop. Our study not only enhances the understanding of the correlation between the cerebellar lobes and ADHD, but also provides an imaging basis for explaining the neural mechanisms underlying ADHD in children.
