Reduced connexin 43 immunolabeling in the orbitofrontal cortex in alcohol dependence and depression

• Published in: Journal of psychiatric research Vol. 55; pp. 101 - 109
• Main Authors: Miguel-Hidalgo, José Javier, Wilson, Barbara A., Hussain, Syed, Meshram, Ashish, Rajkowska, Grazyna, Stockmeier, Craig A.
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 01.08.2014; Elsevier
• Subjects: Addictive behaviors; Adult and adolescent clinical studies; Alcohol dependence; Alcohol-Related Disorders - complications; Alcohol-Related Disorders - metabolism; Alcoholism; Alcoholism and acute alcohol poisoning; Antidepressive Agents - therapeutic use; Biological and medical sciences; Blotting, Western; Comorbidity; Connexin 43 - metabolism; Density; Depression; Depressive Disorder, Major - complications; Depressive Disorder, Major - drug therapy; Depressive Disorder, Major - metabolism; Female; Gap junctions; Gap Junctions - metabolism; Gray Matter - metabolism; Humans; Immunohistochemistry; Major depressive disorder; Male; Medical sciences; Middle Aged; Miscellaneous; Mood disorders; Photomicrography; Postmortem; Prefrontal cortex; Prefrontal Cortex - drug effects; Prefrontal Cortex - metabolism; Proteins; Psychiatry; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Punctum; Time Factors; Toxicology; Immunohistochemistry; Prefrontal cortex; Alcoholism; Gap junctions; Major depressive disorder; Postmortem; Mood disorder; Orbitofrontal cortex; Central nervous system; Cell junction; Depression; Gap junction; Encephalon; Alcoholic beverage; Connexin; Anatomic pathology; Dependence
• DOI: 10.1016/j.jpsychires.2014.04.007
• ISSN: 0022-3956; 1879-1379

Reduced density of glial cells and low levels of some astrocyte proteins have been described in the orbitofrontal cortex (OFC) in depression and alcoholism, two disorders often comorbid. These regressive changes may also involve the communication between astrocytes via gap junctions and hemichannels, which play important regulatory roles in neurotransmission. We determined levels and morphological immunostaining parameters of connexin 43 (Cx43), the main protein subunit of astrocyte gap junctions/hemichannels, in the OFC of subjects with depression, alcoholism or comorbid depression/alcoholism as compared to non-psychiatric subjects. Postmortem brain samples from 23 subjects with major depressive disorder (MDD), 16 with alcohol dependence, 13 with comorbid MDD and alcohol dependence, and 20 psychiatrically-normal comparison subjects were processed for western blots to determine Cx43 levels. Area fraction of Cx43 immunoreactivity, and density and average size of immunoreactive puncta were measured in histological sections. There was a significant, larger than 60 percent decrease in Cx43 level in the three psychiatric groups as compared to controls. Area fraction of immunoreactivity and immunoreactive punctum size were reduced in all psychiatric groups, but Cx43-immunoreactive puncta density was reduced only in alcohol-dependent subjects. Among psychiatric subjects, no difference in Cx43 levels or immunostaining was found between suicides and non-suicides. The present data suggest that dysfunction of the OFC is accompanied by reduction in the levels of gap junction protein Cx43 in depression and alcoholism, and reduction in density of Cx43 immunoreactive puncta only in alcoholism, pointing to altered gap junction or hemichannel-based communication in the pathophysiology of those disorders.