Dysfunction of Astrocyte Connexins 30 and 43 in Dorsal Lateral Prefrontal Cortex of Suicide Completers

被引:126
作者
Ernst, Carl [2 ]
Nagy, Corina
Kim, Sangyheon [4 ]
Yang, Jennie P.
Deng, Xiaoming
Hellstrom, Ian C. [2 ]
Choi, Kwang Ho [4 ]
Gershenfeld, Howard [4 ]
Meaney, Michael J. [2 ,3 ]
Turecki, Gustavo [1 ,2 ,3 ]
机构
[1] McGill Univ, Douglas Hosp Res Ctr, McGill Grp Suicide Studies, Verdun, PQ H4H 1R3, Canada
[2] McGill Univ, Dept Psychiat, Douglas Hosp Res Inst, Verdun, PQ H4H 1R3, Canada
[3] McGill Univ, Sackler Program Epigenet & Psychobiol, Verdun, PQ H4H 1R3, Canada
[4] Univ Texas SW Med Sch, Dept Psychiat, Dallas, TX USA
基金
加拿大自然科学与工程研究理事会;
关键词
Astrocyte; connexin; genetics; prefrontal cortex; Sox9; suicide; FIBRILLARY ACIDIC PROTEIN; MAJOR DEPRESSION; TRANSCRIPTION FACTOR; PRIMARY CULTURES; EXPRESSION; BRAIN; SCHIZOPHRENIA; CALCIUM; SOX9; GENE;
D O I
10.1016/j.biopsych.2011.03.038
中图分类号
Q189 [神经科学];
学科分类号
071006 [神经生物学];
摘要
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.
引用
收藏
页码:312 / 319
页数:8
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