Viral vector transfection systems are among the simplest of biological agents with the ability to transfer genes into the central nervous system. In brain research, a series of powerful and novel gene editing technolo...Viral vector transfection systems are among the simplest of biological agents with the ability to transfer genes into the central nervous system. In brain research, a series of powerful and novel gene editing technologies are based on these systems. Although many viral vectors are used in rodents, their full application has been limited in non-human primates. To identify viral vectors that can stably and effectively express exogenous genes within non- human primates, eleven commonly used recombinant adeno-associated viral and lentiviral vectors, each carrying a gene to express green or red fluorescence, were injected into the parietal cortex of four rhesus monkeys. The expression of fluorescent cells was used to quantify transfection efficiency. Histological results revealed that recombinant adeno-associated viral vectors, especially the serotype 2/9 coupled with the cytomegalovirus, human synapsin I, or Ca2~/calmodulin-dependent protein kinase II promoters, and lentiviral vector coupled with the human ubiquitin C promoter, induced higher expression of fluorescent cells, representing high transfection efficiency. This is the first comparison of transfection efficiencies of different viral vectors carrying different promoters and serotypes in non-human primates （NHPs）. These results can be used as an aid to select optimal vectors to transfer exogenous genes into the central nervous system of non-human primates.展开更多
Auditory verbal hallucination(AVH)is emphasized as a pathological hallmark of schizophrenia.Neuroimaging studies provide evidence linking AVH to overlapping functional abnormalities in distributed networks.However,no ...Auditory verbal hallucination(AVH)is emphasized as a pathological hallmark of schizophrenia.Neuroimaging studies provide evidence linking AVH to overlapping functional abnormalities in distributed networks.However,no clear conclusion has still been reached.This study aimed to further explore the brain activity of patients with schizophrenia having AVH from both local activity(LA)and functional connectivity(FC)insights,while excluding confounding factors from other positive symptoms.A total of 42 patients with AVH(AVH patients group,APG),26 without AVH(non-AVH patients group,NPG),and 82 normal controls(NC)underwent resting-state functional magnetic resonance imaging(fMRI).LA measures,including regional homogeneity(ReHo)and fractional amplitude of low-frequency fluctuations(fALFF),and FC measures were evaluated to understand the neuroimaging mechanism of AVH.APG showed increased ReHo and fALFF in the bilateral putamen(Put)compared with NPG and NC.FC analysis(using bilateral putamen as seeds)revealed that all patients showed abnormal FC of multiple resting state network regions,including the anterior and post cingulate cortex,middle frontal gyrus,inferior parietal gyrus,and left angular gyrus.Interestingly,APG showed significantly decreased FC of insula extending to the superior temporal gyrus and inferior frontal gyrus compared with NPG and NC.The present findings suggested a significant correlation of abnormal LA and dysfunctional putamen-auditory cortical connectivity with the neuropathological mechanism of AVH,providing evidence for the functional disconnection hypothesis of schizophrenia.展开更多
Background： Dysconnectivity hypothesis of schizophrenia has been increasingly emphasized. Recent researches showed that this dysconnectivity might be related to occurrence of auditory hallucination （AH）. However, t...Background： Dysconnectivity hypothesis of schizophrenia has been increasingly emphasized. Recent researches showed that this dysconnectivity might be related to occurrence of auditory hallucination （AH）. However, there is still no consistent conclusion. This study aimed to explore intrinsic dysconnectivity pattern of whole-brain functional networks at voxel level in schizophrenic with AH. Methods： Auditory hallucinated patients group （n = 42 APG）, no hallucinated patients group （n = 42 NPG） and normal controls （n = 84 NCs） were analyzed by resting-state functional magnetic resonance imaging. The functional connectivity metrics index （degree centrality [DC]） across the entire brain networks was calculated and evaluated among three groups. Results： DC decreased in the bilateral putamen and increased in the left superior frontal gyrus in all the patients. However, in APG. the changes of DC were more obvious compared with NPG. Symptomology scores were negatively correlated with the DC of bilateral putamen in all patients. AH score of APG positively correlated with the DC in left superior frontal gyrus but negatively correlated with the DC in bilateral putamen. Conclusion： Our findings corroborated that schizophrenia was characterized by functional dysconnectivity, and the abnormal DC in bilateral putamen and left superior frontal gyrus might be crucial in the occurrence of AH.展开更多
基金supported by the National Program on Key Basic Research Project(973 Programs 2015CB755605)the National Natural Science Foundation of China(81471312)
文摘Viral vector transfection systems are among the simplest of biological agents with the ability to transfer genes into the central nervous system. In brain research, a series of powerful and novel gene editing technologies are based on these systems. Although many viral vectors are used in rodents, their full application has been limited in non-human primates. To identify viral vectors that can stably and effectively express exogenous genes within non- human primates, eleven commonly used recombinant adeno-associated viral and lentiviral vectors, each carrying a gene to express green or red fluorescence, were injected into the parietal cortex of four rhesus monkeys. The expression of fluorescent cells was used to quantify transfection efficiency. Histological results revealed that recombinant adeno-associated viral vectors, especially the serotype 2/9 coupled with the cytomegalovirus, human synapsin I, or Ca2~/calmodulin-dependent protein kinase II promoters, and lentiviral vector coupled with the human ubiquitin C promoter, induced higher expression of fluorescent cells, representing high transfection efficiency. This is the first comparison of transfection efficiencies of different viral vectors carrying different promoters and serotypes in non-human primates （NHPs）. These results can be used as an aid to select optimal vectors to transfer exogenous genes into the central nervous system of non-human primates.
基金'This study was supported by grants from the National 973 Program of China(No.201 lCB707805)the National Natural Science Foundation of China(No.91132301)the Natural Science Foundation of Hubei Province(No.2014CFB732).
文摘Auditory verbal hallucination(AVH)is emphasized as a pathological hallmark of schizophrenia.Neuroimaging studies provide evidence linking AVH to overlapping functional abnormalities in distributed networks.However,no clear conclusion has still been reached.This study aimed to further explore the brain activity of patients with schizophrenia having AVH from both local activity(LA)and functional connectivity(FC)insights,while excluding confounding factors from other positive symptoms.A total of 42 patients with AVH(AVH patients group,APG),26 without AVH(non-AVH patients group,NPG),and 82 normal controls(NC)underwent resting-state functional magnetic resonance imaging(fMRI).LA measures,including regional homogeneity(ReHo)and fractional amplitude of low-frequency fluctuations(fALFF),and FC measures were evaluated to understand the neuroimaging mechanism of AVH.APG showed increased ReHo and fALFF in the bilateral putamen(Put)compared with NPG and NC.FC analysis(using bilateral putamen as seeds)revealed that all patients showed abnormal FC of multiple resting state network regions,including the anterior and post cingulate cortex,middle frontal gyrus,inferior parietal gyrus,and left angular gyrus.Interestingly,APG showed significantly decreased FC of insula extending to the superior temporal gyrus and inferior frontal gyrus compared with NPG and NC.The present findings suggested a significant correlation of abnormal LA and dysfunctional putamen-auditory cortical connectivity with the neuropathological mechanism of AVH,providing evidence for the functional disconnection hypothesis of schizophrenia.
基金Financial support and sponsorship This research was supported by grants from the National 973 Program of China （No. 2011CB707805）, and the National Natural Science Foundation of China （No. 91132301）, and the Natural Science Foundation of Hubei Province （No. 2014CFB732）.
文摘Background： Dysconnectivity hypothesis of schizophrenia has been increasingly emphasized. Recent researches showed that this dysconnectivity might be related to occurrence of auditory hallucination （AH）. However, there is still no consistent conclusion. This study aimed to explore intrinsic dysconnectivity pattern of whole-brain functional networks at voxel level in schizophrenic with AH. Methods： Auditory hallucinated patients group （n = 42 APG）, no hallucinated patients group （n = 42 NPG） and normal controls （n = 84 NCs） were analyzed by resting-state functional magnetic resonance imaging. The functional connectivity metrics index （degree centrality [DC]） across the entire brain networks was calculated and evaluated among three groups. Results： DC decreased in the bilateral putamen and increased in the left superior frontal gyrus in all the patients. However, in APG. the changes of DC were more obvious compared with NPG. Symptomology scores were negatively correlated with the DC of bilateral putamen in all patients. AH score of APG positively correlated with the DC in left superior frontal gyrus but negatively correlated with the DC in bilateral putamen. Conclusion： Our findings corroborated that schizophrenia was characterized by functional dysconnectivity, and the abnormal DC in bilateral putamen and left superior frontal gyrus might be crucial in the occurrence of AH.
基金supported by the Key-Area Research and Development Program of Guangdong Province (2019B03035001)the National Natural Science Foundation of China (81941014, 31625013, 91732302, 81471312, 81771387, 81460352, 81500983, 31700897, 31700910, 31800901, 31700897, 31960178, and 81460352)+7 种基金the Strategic Priority Research Program of the Chinese Academy of Sciences (XDBS32060200)the Shanghai Brain-Intelligence Project from the Science and Technology Commission of the Shanghai Municipality (16JC1420501)the Shanghai Municipal Science and Technology Major Project (2018SHZDZX05)the Applied Basic Research Programs of Science and Technology Commission Foundation of Yunnan Province (2017FB109, 2018FB052, 2018FB053, and 2019FA007)the China Postdoctoral Science Foundation (2018M631105)the CAS ‘‘Light of West China” Programthe National Key R&D Program of China (2018YFA0801403)the Key Scientific and Technological Projects of Guangdong Province (2018B030335001)。
