Schizophrenia is a disease that affects many areas of the brain. The dopamine hypothesis is one of the most widely-accepted ideas in the pathophysiology of schizophrenia. Besides alterations in the dopaminergic system...Schizophrenia is a disease that affects many areas of the brain. The dopamine hypothesis is one of the most widely-accepted ideas in the pathophysiology of schizophrenia. Besides alterations in the dopaminergic system in the central nervous system, there have been several reports of changes in dopaminergic systems in the peripheral blood of schizophrenic patients. Several reports have shown that dopamine receptor expression by lymphocytes is altered in patients with schizophrenia, but the results have been conflicting. We therefore re-assessed D3R and D4R mRNA levels in 11 patients with schizophrenia and 12 healthy subjects and correlated levels with severity of symptoms. D3R and D4R expression in lymphocytes and granulocytes was measured by quantitative RT-PCR and the severity of symptoms and cognitive impairment were assessed using the PANSS and BACS-J. There were no significant differences in mean D3R or D4R mRNA levels in lymphocytes from schizophrenic patients and controls and no significant difference in mean D4R mRNA levels in granulocytes (D3R mRNA undetectable). In patients with schizophrenia, D3R expression was inversely correlated with the total PANSS score (r = 0.768, p = 0.009), while D4R expression was positively correlated with working memory scales (r = 0.895, p = 0.001). In conclusion, these results imply that lymphocyte D3R and D4R are involved in the mechanisms of the disorder and could be used as target markers in the treatment of schizophrenia.展开更多
The dopaminergic system controls several vital central nervous system functions,including the control of movement,reward behaviors and cognition.Alterations of dopaminergic signaling are involved in the pathogenesis o...The dopaminergic system controls several vital central nervous system functions,including the control of movement,reward behaviors and cognition.Alterations of dopaminergic signaling are involved in the pathogenesis of neurodegenerative and psychiatric disorders,in particular Parkinson’s disease,which are associated with a subtle and chronic inflammatory response.A substantial body of evidence has demonstrated the non-neuronal expression of dopamine,its receptors and of the machinery that governs synthesis,secretion and storage of dopamine across several immune cell types.This review aims to summarize current knowledge on the role and expression of dopamine in immune cells.One of the goals is to decipher the complex mechanisms through which these cell types respond to dopamine,in order to address the impact this has on neurodegenerative and psychiatric pathologies such as Parkinson’s disease.A further aim is to illustrate the gaps in our understanding of the physiological roles of dopamine to encourage more targeted research focused on understanding the consequences of aberrant dopamine production on immune regulation.These highlights may prompt scientists in the field to consider alternative functions of this important neurotransmitter when targeting neuroinflammatory/neurodegenerative pathologies.展开更多
左旋苯丙胺(又称左苯丙胺,RAT)在临床上被用于治疗多种病症,作用在中枢神经细胞多巴胺受体上,同时它具有依赖性和成瘾性。为了探讨RAT被用作药物的药理和成瘾机制,本文用分子模拟获得RAT与多巴胺第三受体(D_3R)复合蛋白优化结构,并且采...左旋苯丙胺(又称左苯丙胺,RAT)在临床上被用于治疗多种病症,作用在中枢神经细胞多巴胺受体上,同时它具有依赖性和成瘾性。为了探讨RAT被用作药物的药理和成瘾机制,本文用分子模拟获得RAT与多巴胺第三受体(D_3R)复合蛋白优化结构,并且采用伞形样本平均力势(PMF)方法和卵磷脂脂质分子模拟生物膜,采用分子动力学模拟获得RAT在D_3R结构中分子通道运动轨迹和自由能变化。RAT通过D_3R结构中的功能分子通道,朝细胞外方向传输运动的自由能变化为91.4 k J?mol^(-1)。RAT通过D_3R结构中的保护分子通道,朝细胞双层膜方向传输运动的自由能变化为117.7 k J?mol^(-1)。自由能数值表明RAT分子更容易通过D_3R结构中的功能分子通道,发挥其功能作用,增大功能多巴胺分子的释放,导致包括依赖性和成瘾性多种功能效果。研究结果证明RAT被用作药物的药理和成瘾机制与它在多巴胺受体中的分子通道上传输动力学和机制有密切关联。展开更多
Because behavior recognition is based on video frame sequences,this paper proposes a behavior recognition algorithm that combines 3D residual convolutional neural network(R3D)and long short-term memory(LSTM).First,the...Because behavior recognition is based on video frame sequences,this paper proposes a behavior recognition algorithm that combines 3D residual convolutional neural network(R3D)and long short-term memory(LSTM).First,the residual module is extended to three dimensions,which can extract features in the time and space domain at the same time.Second,by changing the size of the pooling layer window the integrity of the time domain features is preserved,at the same time,in order to overcome the difficulty of network training and over-fitting problems,the batch normalization(BN)layer and the dropout layer are added.After that,because the global average pooling layer(GAP)is affected by the size of the feature map,the network cannot be further deepened,so the convolution layer and maxpool layer are added to the R3D network.Finally,because LSTM has the ability to memorize information and can extract more abstract timing features,the LSTM network is introduced into the R3D network.Experimental results show that the R3D+LSTM network achieves 91%recognition rate on the UCF-101 dataset.展开更多
文摘Schizophrenia is a disease that affects many areas of the brain. The dopamine hypothesis is one of the most widely-accepted ideas in the pathophysiology of schizophrenia. Besides alterations in the dopaminergic system in the central nervous system, there have been several reports of changes in dopaminergic systems in the peripheral blood of schizophrenic patients. Several reports have shown that dopamine receptor expression by lymphocytes is altered in patients with schizophrenia, but the results have been conflicting. We therefore re-assessed D3R and D4R mRNA levels in 11 patients with schizophrenia and 12 healthy subjects and correlated levels with severity of symptoms. D3R and D4R expression in lymphocytes and granulocytes was measured by quantitative RT-PCR and the severity of symptoms and cognitive impairment were assessed using the PANSS and BACS-J. There were no significant differences in mean D3R or D4R mRNA levels in lymphocytes from schizophrenic patients and controls and no significant difference in mean D4R mRNA levels in granulocytes (D3R mRNA undetectable). In patients with schizophrenia, D3R expression was inversely correlated with the total PANSS score (r = 0.768, p = 0.009), while D4R expression was positively correlated with working memory scales (r = 0.895, p = 0.001). In conclusion, these results imply that lymphocyte D3R and D4R are involved in the mechanisms of the disorder and could be used as target markers in the treatment of schizophrenia.
基金supported by a Research Development Fund(UTS Start-Up Grant 2018)from the University of Technology Sydney to AC。
文摘The dopaminergic system controls several vital central nervous system functions,including the control of movement,reward behaviors and cognition.Alterations of dopaminergic signaling are involved in the pathogenesis of neurodegenerative and psychiatric disorders,in particular Parkinson’s disease,which are associated with a subtle and chronic inflammatory response.A substantial body of evidence has demonstrated the non-neuronal expression of dopamine,its receptors and of the machinery that governs synthesis,secretion and storage of dopamine across several immune cell types.This review aims to summarize current knowledge on the role and expression of dopamine in immune cells.One of the goals is to decipher the complex mechanisms through which these cell types respond to dopamine,in order to address the impact this has on neurodegenerative and psychiatric pathologies such as Parkinson’s disease.A further aim is to illustrate the gaps in our understanding of the physiological roles of dopamine to encourage more targeted research focused on understanding the consequences of aberrant dopamine production on immune regulation.These highlights may prompt scientists in the field to consider alternative functions of this important neurotransmitter when targeting neuroinflammatory/neurodegenerative pathologies.
文摘左旋苯丙胺(又称左苯丙胺,RAT)在临床上被用于治疗多种病症,作用在中枢神经细胞多巴胺受体上,同时它具有依赖性和成瘾性。为了探讨RAT被用作药物的药理和成瘾机制,本文用分子模拟获得RAT与多巴胺第三受体(D_3R)复合蛋白优化结构,并且采用伞形样本平均力势(PMF)方法和卵磷脂脂质分子模拟生物膜,采用分子动力学模拟获得RAT在D_3R结构中分子通道运动轨迹和自由能变化。RAT通过D_3R结构中的功能分子通道,朝细胞外方向传输运动的自由能变化为91.4 k J?mol^(-1)。RAT通过D_3R结构中的保护分子通道,朝细胞双层膜方向传输运动的自由能变化为117.7 k J?mol^(-1)。自由能数值表明RAT分子更容易通过D_3R结构中的功能分子通道,发挥其功能作用,增大功能多巴胺分子的释放,导致包括依赖性和成瘾性多种功能效果。研究结果证明RAT被用作药物的药理和成瘾机制与它在多巴胺受体中的分子通道上传输动力学和机制有密切关联。
基金Supported by the Shaanxi Province Key Research and Development Project (No. 2021GY-280)Shaanxi Province Natural Science Basic Research Program (No. 2021JM-459)the National Natural Science Foundation of China (No. 61772417)
文摘Because behavior recognition is based on video frame sequences,this paper proposes a behavior recognition algorithm that combines 3D residual convolutional neural network(R3D)and long short-term memory(LSTM).First,the residual module is extended to three dimensions,which can extract features in the time and space domain at the same time.Second,by changing the size of the pooling layer window the integrity of the time domain features is preserved,at the same time,in order to overcome the difficulty of network training and over-fitting problems,the batch normalization(BN)layer and the dropout layer are added.After that,because the global average pooling layer(GAP)is affected by the size of the feature map,the network cannot be further deepened,so the convolution layer and maxpool layer are added to the R3D network.Finally,because LSTM has the ability to memorize information and can extract more abstract timing features,the LSTM network is introduced into the R3D network.Experimental results show that the R3D+LSTM network achieves 91%recognition rate on the UCF-101 dataset.
