Aims: We focused on DNA methylation of the promoter regions of the Monoamine Oxidase (MAO) A and B genes from postmortem brains of subjects with schizophrenia. Methods: We determined levels of DNA methylation using ge...Aims: We focused on DNA methylation of the promoter regions of the Monoamine Oxidase (MAO) A and B genes from postmortem brains of subjects with schizophrenia. Methods: We determined levels of DNA methylation using genomic DNA samples purified from four brain areas: prefrontal cortex (PFC), hippocampus, occipital cortex and nucleus accumbens (NAc), by a bisulfite sequencing method from seven normal subjects and six subjects with schizophrenia. Results: Although very few methylated CpGs of the MAOA and MAOB genes were detected in male samples, various DNA methylation patterns were present in female samples, and some differences were found in such patterns between normal subjects and subjects with schizophrenia. In the PFC, the average level of methylation of both genes was significantly higher in subjects with schizophrenia than in normal subjects. The content of highly methylated alleles of the MAOA gene in the NAc was significantly associated with schizophrenia, with similar results obtained for the MAOB gene in both the NAc and PFC. Some CpG sites showed higher levels of methylation in schizophrenia than in normal subjects. Conclusions: Levels of methylation were quite high in NAc and PFC in female subjects with schizophrenia compared with those in female normal subjects.展开更多
In this study, we sought to elucidate the process of DNA degradation in brain and dental pulp cells of mice, within postmortem 0-72 hours, by using the single cell gel electrophoresis assay and professional comet imag...In this study, we sought to elucidate the process of DNA degradation in brain and dental pulp cells of mice, within postmortem 0-72 hours, by using the single cell gel electrophoresis assay and professional comet image analysis and processing techniques. The frequency of comet-like cells, the percentage of tail DNA, tail length, tail moment, Olive moment and tail area increased in tandem with increasing postmortem interval. In contrast, the head radius, the percentage of head DNA and head area showed a decreasing trend. Linear regression analysis revealed a high correlation between these parameters and the postmortem interval. The findings suggest that the single cell gel electrophoresis assay is a quick and sensitive method to detect DNA degradation in brain and dental pulp cells, providing an objective and accurate new way to estimate postmortem interval.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
文摘Aims: We focused on DNA methylation of the promoter regions of the Monoamine Oxidase (MAO) A and B genes from postmortem brains of subjects with schizophrenia. Methods: We determined levels of DNA methylation using genomic DNA samples purified from four brain areas: prefrontal cortex (PFC), hippocampus, occipital cortex and nucleus accumbens (NAc), by a bisulfite sequencing method from seven normal subjects and six subjects with schizophrenia. Results: Although very few methylated CpGs of the MAOA and MAOB genes were detected in male samples, various DNA methylation patterns were present in female samples, and some differences were found in such patterns between normal subjects and subjects with schizophrenia. In the PFC, the average level of methylation of both genes was significantly higher in subjects with schizophrenia than in normal subjects. The content of highly methylated alleles of the MAOA gene in the NAc was significantly associated with schizophrenia, with similar results obtained for the MAOB gene in both the NAc and PFC. Some CpG sites showed higher levels of methylation in schizophrenia than in normal subjects. Conclusions: Levels of methylation were quite high in NAc and PFC in female subjects with schizophrenia compared with those in female normal subjects.
基金supported by Key Research Plan of the Ministry of Public Security of China, No. 2011ZDYJXJXY005Scientific Research Foundation of the Higher Education Institutions of Liaoning Province, China, No. 2008Z205
文摘In this study, we sought to elucidate the process of DNA degradation in brain and dental pulp cells of mice, within postmortem 0-72 hours, by using the single cell gel electrophoresis assay and professional comet image analysis and processing techniques. The frequency of comet-like cells, the percentage of tail DNA, tail length, tail moment, Olive moment and tail area increased in tandem with increasing postmortem interval. In contrast, the head radius, the percentage of head DNA and head area showed a decreasing trend. Linear regression analysis revealed a high correlation between these parameters and the postmortem interval. The findings suggest that the single cell gel electrophoresis assay is a quick and sensitive method to detect DNA degradation in brain and dental pulp cells, providing an objective and accurate new way to estimate postmortem interval.
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.
