The prefrontal neocortex is involved in many high cognitive functions in humans.Deficits in neuronal and neurocircuitry development in this part of the cerebrum have been associated with various neuropsychiatric disor...The prefrontal neocortex is involved in many high cognitive functions in humans.Deficits in neuronal and neurocircuitry development in this part of the cerebrum have been associated with various neuropsychiatric disorders in adolescents and adults.There are currently little available data regarding prenatal dendrite and spine formation on projecting neurons in the human prefrontal neocortex.Previous studies have demonstrated that Golgi silver staining can identify neurons in the frontal lobe and visual cortex in human embryos.In the present study,five fetal brains,at 19,20,26,35,and 38 gestational weeks,were obtained via the body donation program at Xiangya School of Medicine,Central South University,China.Golgi-stained pyramidal neurons in layer V of Brodmann area 46 in fetuses were quantitatively analyzed using the Neurolucida morphometry system.Results revealed that somal size,total dendritic length,and branching points of these neurons increased from 26 to 38 gestational weeks.There was also a large increase in dendritic spines from 35 to 38 gestational weeks.These findings indicate that,in the human prefrontal neocortex,dendritic growth in layer V pyramidal neurons occurs rapidly during the third trimester of gestation.The use of human fetal brain tissue was approved by the Animal Ethics Committee of Xiangya School of Medicine,Central South University,China(approval No.2011-045)on April 5,2011.展开更多
Advances in cellular and molecular biology underpin most current therapeutic advances in medicine.Such advances for neurological and neurodegenerative diseases are hindered by the lack of similar specimens. It is beco...Advances in cellular and molecular biology underpin most current therapeutic advances in medicine.Such advances for neurological and neurodegenerative diseases are hindered by the lack of similar specimens. It is becoming increasingly evident that greater access to human brain tissue is necessary to understand both the cellular biology of these diseases and their variation. Research in these areas is vital to the development of viable therapeutic options for these currently untreatable diseases. The development and coordination of human brain specimen collection through brain banks is evolving. This perspective article from the Sydney Brain Bank reviews data concerning the best ways to collect and store material for different research purposes.展开更多
Investigating the pathophysiological mechanisms underlying brain disorders is a priority if novel therapeutic strategies are to be developed. In vivo studies of animal models and in vitro studies of cell lines/primary...Investigating the pathophysiological mechanisms underlying brain disorders is a priority if novel therapeutic strategies are to be developed. In vivo studies of animal models and in vitro studies of cell lines/primary cell cultures may provide useful tools to study certain aspects of brain disorders. However, discrepancies among these studies or unsuccessful translation from animal/cell studies to human/clinical studies often occur, because these models generally represent only some symptoms of a neuropsychiatric disorder rather than the complete disorder. Human brain slice cultures from postmortem tissue or resected tissue from operations have shown that, in vitro, neurons and glia can stay alive for long periods of time, while their morphological and physiological characteristics, and their ability to respond to experimental manipulations are maintained. Human brain slices can thus provide a close representation of neuronal networks in vivo, be a valuable tool for investigation of the basis of neuropsychiatric disorders, and provide a platform for the evaluation of novel pharmacological treatments of human brain diseases.A brain bank needs to provide the necessary infrastructure to bring together donors, hospitals, and researchers who want to investigate human brain slices in cultures of clinically and neuropathologically well-documented material.展开更多
In this study, the distribution of five Alzheimer's disease(AD)-related single nucleotide polymorphisms(SNPs) in the Han population was examined in combination with the evaluation of clinical cognition and brain p...In this study, the distribution of five Alzheimer's disease(AD)-related single nucleotide polymorphisms(SNPs) in the Han population was examined in combination with the evaluation of clinical cognition and brain pathological analysis. The associations among SNPs,clinical daily cognitive states, and postmortem neuropathological changes were analyzed in 110 human brains from the Chinese Academy of Medical Sciences/Peking Union Medical College(CAMS/PUMC) Human Brain Bank.APOE ?4(OR = 4.482, P = 0.004), the RS2305421 GG genotype(adjusted OR = 4.397, P = 0.015), and the RS10498633 GT genotype(adjusted OR = 2.375,P = 0.028) were associated with a higher score on the ABC(Ab plaque score, Braak NFT stage, and CERAD neuritic plaque score) dementia scale. These results advance our understanding of the pathogenesis of AD,the relationship between pathological diagnosis and clinical diagnosis, and the SNPs in the Han population for future research.展开更多
Amyloid beta(Aβ)plaques are one of the hallmarks of Alzheimer’s disease(AD).However,currently available anti-amyloid therapies fail to show effectiveness in the treatment of AD in humans.It has been found that there...Amyloid beta(Aβ)plaques are one of the hallmarks of Alzheimer’s disease(AD).However,currently available anti-amyloid therapies fail to show effectiveness in the treatment of AD in humans.It has been found that there are different types of Aβplaque(diffuse and focal types)in the postmortem human brain.In this study,we aimed to investigate the correlations among different types of Aβplaque and AD-related neuropathological and cognitive changes based on a postmortem human brain bank in China.The results indicated that focal plaques,but not diffuse plaques,significantly increased with age in the human hippocampus.We also found that the number of focal plaques was positively correlated with the severity of AD-related neuropathological changes(measured by the“ABC”scoring system)and cognitive decline(measured by the Everyday Cognitive Insider Questionnaire).Furthermore,most of the focal plaques were co-localized with neuritic plaques(identified by Bielschowsky silver staining)and accompanied by microglial and other inflammatory cells.Our findings suggest the potential of using focal-type but not general Aβplaques as biomarkers for the neuropathological evaluation of AD.展开更多
基金supported by the National Natural Science Foundation of China,No.81873780(to DHL)grants from the Department of Education of Hunan Province of China,No.16C1577(to LXH)the Xiangtan Medicine and Health Vocational College of China
文摘The prefrontal neocortex is involved in many high cognitive functions in humans.Deficits in neuronal and neurocircuitry development in this part of the cerebrum have been associated with various neuropsychiatric disorders in adolescents and adults.There are currently little available data regarding prenatal dendrite and spine formation on projecting neurons in the human prefrontal neocortex.Previous studies have demonstrated that Golgi silver staining can identify neurons in the frontal lobe and visual cortex in human embryos.In the present study,five fetal brains,at 19,20,26,35,and 38 gestational weeks,were obtained via the body donation program at Xiangya School of Medicine,Central South University,China.Golgi-stained pyramidal neurons in layer V of Brodmann area 46 in fetuses were quantitatively analyzed using the Neurolucida morphometry system.Results revealed that somal size,total dendritic length,and branching points of these neurons increased from 26 to 38 gestational weeks.There was also a large increase in dendritic spines from 35 to 38 gestational weeks.These findings indicate that,in the human prefrontal neocortex,dendritic growth in layer V pyramidal neurons occurs rapidly during the third trimester of gestation.The use of human fetal brain tissue was approved by the Animal Ethics Committee of Xiangya School of Medicine,Central South University,China(approval No.2011-045)on April 5,2011.
基金funding for the facility from the University of New South Wales and Neuroscience Research Australia
文摘Advances in cellular and molecular biology underpin most current therapeutic advances in medicine.Such advances for neurological and neurodegenerative diseases are hindered by the lack of similar specimens. It is becoming increasingly evident that greater access to human brain tissue is necessary to understand both the cellular biology of these diseases and their variation. Research in these areas is vital to the development of viable therapeutic options for these currently untreatable diseases. The development and coordination of human brain specimen collection through brain banks is evolving. This perspective article from the Sydney Brain Bank reviews data concerning the best ways to collect and store material for different research purposes.
基金supported by the National Natural Science Foundation of China (81501172)the China Exchange Programme of the Royal Netherlands Academy of Arts and Sciences (10CDP0037 and 05CD9027)+3 种基金the Shanghai Municipal Commission of Health and Family Planning (20154Y0016)an Innovation Project of the Chinese Academy of Sciences (KSCX2-SW-217)a National Basic Research Development Program of China (2006CB500705)the Internationale Stichting Alzheimer Onderzoek (05501)
文摘Investigating the pathophysiological mechanisms underlying brain disorders is a priority if novel therapeutic strategies are to be developed. In vivo studies of animal models and in vitro studies of cell lines/primary cell cultures may provide useful tools to study certain aspects of brain disorders. However, discrepancies among these studies or unsuccessful translation from animal/cell studies to human/clinical studies often occur, because these models generally represent only some symptoms of a neuropsychiatric disorder rather than the complete disorder. Human brain slice cultures from postmortem tissue or resected tissue from operations have shown that, in vitro, neurons and glia can stay alive for long periods of time, while their morphological and physiological characteristics, and their ability to respond to experimental manipulations are maintained. Human brain slices can thus provide a close representation of neuronal networks in vivo, be a valuable tool for investigation of the basis of neuropsychiatric disorders, and provide a platform for the evaluation of novel pharmacological treatments of human brain diseases.A brain bank needs to provide the necessary infrastructure to bring together donors, hospitals, and researchers who want to investigate human brain slices in cultures of clinically and neuropathologically well-documented material.
基金supported by grants from the National Natural Science Foundation of China(81271239,81771205,and 91632113)the Institute of Basic Medical Sciences/Chinese Academy of Medical Sciences(CAMS)Dean’s Fund(2011RC01)+1 种基金the CAMS Innovation Fund for Medical Sciences(2016-I2M-1004)the Natural Science Foundation and Major Basic Research Program of Shanghai Municipality,China(16JC1420500 and 16JC1420502)
文摘In this study, the distribution of five Alzheimer's disease(AD)-related single nucleotide polymorphisms(SNPs) in the Han population was examined in combination with the evaluation of clinical cognition and brain pathological analysis. The associations among SNPs,clinical daily cognitive states, and postmortem neuropathological changes were analyzed in 110 human brains from the Chinese Academy of Medical Sciences/Peking Union Medical College(CAMS/PUMC) Human Brain Bank.APOE ?4(OR = 4.482, P = 0.004), the RS2305421 GG genotype(adjusted OR = 4.397, P = 0.015), and the RS10498633 GT genotype(adjusted OR = 2.375,P = 0.028) were associated with a higher score on the ABC(Ab plaque score, Braak NFT stage, and CERAD neuritic plaque score) dementia scale. These results advance our understanding of the pathogenesis of AD,the relationship between pathological diagnosis and clinical diagnosis, and the SNPs in the Han population for future research.
基金This work was supported by grants from the National Natural Science Foundation of China(81771205 and 81801114)the CAMS Innovation Fund for Medical Sciences(2021-I2M-1-025)Science Innovation 2030–Brain Science and BrainInspired Intelligence Technology Major Project(2021ZD0201100 and 2021ZD0201101).We thank Dr.Xiaojin Qian and Dr.Yongmei Chen(Department of Anatomy,Histology and Embryology,Institute of Basic Medical Sciences,Chinese Academy of Medical Sciences)for technical assistance in immunohistochemistry.
文摘Amyloid beta(Aβ)plaques are one of the hallmarks of Alzheimer’s disease(AD).However,currently available anti-amyloid therapies fail to show effectiveness in the treatment of AD in humans.It has been found that there are different types of Aβplaque(diffuse and focal types)in the postmortem human brain.In this study,we aimed to investigate the correlations among different types of Aβplaque and AD-related neuropathological and cognitive changes based on a postmortem human brain bank in China.The results indicated that focal plaques,but not diffuse plaques,significantly increased with age in the human hippocampus.We also found that the number of focal plaques was positively correlated with the severity of AD-related neuropathological changes(measured by the“ABC”scoring system)and cognitive decline(measured by the Everyday Cognitive Insider Questionnaire).Furthermore,most of the focal plaques were co-localized with neuritic plaques(identified by Bielschowsky silver staining)and accompanied by microglial and other inflammatory cells.Our findings suggest the potential of using focal-type but not general Aβplaques as biomarkers for the neuropathological evaluation of AD.
