Dysfunction of Astrocyte Connexins 30 and 43 in Dorsal Lateral Prefrontal Cortex of Suicide Completers
Background Suicide is an important public health problem that results from the interaction of both psychosocial and biological factors. Although it is known that particular neurobiological processes underlie suicidal ideation and behavior, there still remains limited knowledge about the specific fac...
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Published in | Biological psychiatry (1969) Vol. 70; no. 4; pp. 312 - 319 |
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Main Authors | , , , , , , , , , |
Format | Journal Article |
Language | English |
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Elsevier Inc
15.08.2011
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Abstract | Background Suicide is an important public health problem that results from the interaction of both psychosocial and biological factors. Although it is known that particular neurobiological processes underlie suicidal ideation and behavior, there still remains limited knowledge about the specific factors involved. Methods To explore the neurobiology of suicide we generated microarray data from dorsal lateral prefrontal cortex (DLPFC) in each of 28 male French-Canadian subjects (20 suicide completers). These results were followed up in a larger French-Canadian sample ( n = 47, 38 suicide completers) and in microarray data available from the Stanley Foundation ( n = 100, 36 suicide completers). To investigate the molecular mechanisms of this finding, we performed RNA interference and electrophoretic mobility shift assays. Animal behavioral experiments were done to control for drug and alcohol effects. Results We found reduced expression of Cx30 and Cx43 in DLPFC of suicide completers. We identified a previously unknown function for Sox9 as a transcription factor affecting expression of Cx30 in brain. Conclusions These results suggest that alterations of astrocyte connexins might be involved in the suicide process and provide further evidence implicating astrocytes in psychopathology. |
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AbstractList | Background Suicide is an important public health problem that results from the interaction of both psychosocial and biological factors. Although it is known that particular neurobiological processes underlie suicidal ideation and behavior, there still remains limited knowledge about the specific factors involved. Methods To explore the neurobiology of suicide we generated microarray data from dorsal lateral prefrontal cortex (DLPFC) in each of 28 male French-Canadian subjects (20 suicide completers). These results were followed up in a larger French-Canadian sample ( n = 47, 38 suicide completers) and in microarray data available from the Stanley Foundation ( n = 100, 36 suicide completers). To investigate the molecular mechanisms of this finding, we performed RNA interference and electrophoretic mobility shift assays. Animal behavioral experiments were done to control for drug and alcohol effects. Results We found reduced expression of Cx30 and Cx43 in DLPFC of suicide completers. We identified a previously unknown function for Sox9 as a transcription factor affecting expression of Cx30 in brain. Conclusions These results suggest that alterations of astrocyte connexins might be involved in the suicide process and provide further evidence implicating astrocytes in psychopathology. BACKGROUNDSuicide is an important public health problem that results from the interaction of both psychosocial and biological factors. Although it is known that particular neurobiological processes underlie suicidal ideation and behavior, there still remains limited knowledge about the specific factors involved.METHODSTo explore the neurobiology of suicide we generated microarray data from dorsal lateral prefrontal cortex (DLPFC) in each of 28 male French-Canadian subjects (20 suicide completers). These results were followed up in a larger French-Canadian sample (n = 47, 38 suicide completers) and in microarray data available from the Stanley Foundation (n = 100, 36 suicide completers). To investigate the molecular mechanisms of this finding, we performed RNA interference and electrophoretic mobility shift assays. Animal behavioral experiments were done to control for drug and alcohol effects.RESULTSWe found reduced expression of Cx30 and Cx43 in DLPFC of suicide completers. We identified a previously unknown function for Sox9 as a transcription factor affecting expression of Cx30 in brain.CONCLUSIONSThese results suggest that alterations of astrocyte connexins might be involved in the suicide process and provide further evidence implicating astrocytes in psychopathology. Suicide is an important public health problem that results from the interaction of both psychosocial and biological factors. Although it is known that particular neurobiological processes underlie suicidal ideation and behavior, there still remains limited knowledge about the specific factors involved. To explore the neurobiology of suicide we generated microarray data from dorsal lateral prefrontal cortex (DLPFC) in each of 28 male French-Canadian subjects (20 suicide completers). These results were followed up in a larger French-Canadian sample ( n = 47, 38 suicide completers) and in microarray data available from the Stanley Foundation ( n = 100, 36 suicide completers). To investigate the molecular mechanisms of this finding, we performed RNA interference and electrophoretic mobility shift assays. Animal behavioral experiments were done to control for drug and alcohol effects. We found reduced expression of Cx30 and Cx43 in DLPFC of suicide completers. We identified a previously unknown function for Sox9 as a transcription factor affecting expression of Cx30 in brain. These results suggest that alterations of astrocyte connexins might be involved in the suicide process and provide further evidence implicating astrocytes in psychopathology. Suicide is an important public health problem that results from the interaction of both psychosocial and biological factors. Although it is known that particular neurobiological processes underlie suicidal ideation and behavior, there still remains limited knowledge about the specific factors involved. To explore the neurobiology of suicide we generated microarray data from dorsal lateral prefrontal cortex (DLPFC) in each of 28 male French-Canadian subjects (20 suicide completers). These results were followed up in a larger French-Canadian sample (n = 47, 38 suicide completers) and in microarray data available from the Stanley Foundation (n = 100, 36 suicide completers). To investigate the molecular mechanisms of this finding, we performed RNA interference and electrophoretic mobility shift assays. Animal behavioral experiments were done to control for drug and alcohol effects. We found reduced expression of Cx30 and Cx43 in DLPFC of suicide completers. We identified a previously unknown function for Sox9 as a transcription factor affecting expression of Cx30 in brain. These results suggest that alterations of astrocyte connexins might be involved in the suicide process and provide further evidence implicating astrocytes in psychopathology. |
Author | Gershenfeld, Howard Nagy, Corina Choi, Kwang Ho Meaney, Michael J Yang, Jennie P Ernst, Carl Turecki, Gustavo Deng, Xiaoming Hellstrom, Ian C Kim, Sangyheon |
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BackLink | https://www.ncbi.nlm.nih.gov/pubmed/21571253$$D View this record in MEDLINE/PubMed |
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Keywords | Sox9 genetics Astrocyte prefrontal cortex connexin suicide |
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Snippet | Background Suicide is an important public health problem that results from the interaction of both psychosocial and biological factors. Although it is known... Suicide is an important public health problem that results from the interaction of both psychosocial and biological factors. Although it is known that... BACKGROUNDSuicide is an important public health problem that results from the interaction of both psychosocial and biological factors. Although it is known... |
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SubjectTerms | Adult Animals Astrocyte Astrocytes - metabolism Cell Line, Transformed connexin Connexin 30 Connexin 43 - genetics Connexin 43 - metabolism Connexins - genetics Connexins - metabolism Electrophoretic Mobility Shift Assay Female Gene Expression Regulation - genetics genetics Humans Male Microarray Analysis - methods Middle Aged prefrontal cortex Prefrontal Cortex - pathology Protein Binding - genetics Psychiatry Quebec - ethnology Rats RNA, Small Interfering - genetics RNA, Small Interfering - metabolism Sox9 SOX9 Transcription Factor - genetics SOX9 Transcription Factor - metabolism Suicide Time Factors Transfection - methods |
Title | Dysfunction of Astrocyte Connexins 30 and 43 in Dorsal Lateral Prefrontal Cortex of Suicide Completers |
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