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

Abstract

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.