Reduced connexin 43 immunolabeling in the orbitofrontal cortex in alcohol dependence and depression.
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.
Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, 2500 N. State Street, Jackson, MS 39216-4505, USA. Electronic address: jmiguel-hidalgo@umc.edu.
José Javier
JJ
Miguel-Hidalgo
Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, 2500 N. State Street, Jackson, MS 39216-4505, USA.
Barbara A
BA
Wilson
Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, 2500 N. State Street, Jackson, MS 39216-4505, USA.
Syed
S
Hussain
Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, 2500 N. State Street, Jackson, MS 39216-4505, USA.
Ashish
A
Meshram
Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, 2500 N. State Street, Jackson, MS 39216-4505, USA.
Grazyna
G
Rajkowska
Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, 2500 N. State Street, Jackson, MS 39216-4505, USA; Psychiatry, Case Western Reserve University, Cleveland, OH, USA.
Craig A
CA
Stockmeier
D019973:Alcohol-Related Disorders / Q000150:complications / Q000378:metabolism*; D000928:Antidepressive Agents / Q000627:therapeutic use; D015153:Blotting, Western; D015897:Comorbidity; D018031:Connexin 43 / Q000378:metabolism*; D003865:Major Depressive Disorder / Q000150:complications / Q000188:drug therapy / Q000378:metabolism*; D005260:Female; D017629:Gap Junctions / Q000378:metabolism; D066128:Gray Matter / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D010784:Photomicrography; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism*; D013997:Time Factors
D000928:Antidepressive Agents; D018031:Connexin 43; C500216:GJA1 protein, human
Alcoholism; Gap junctions; Immunohistochemistry; Major depressive disorder; Postmortem; Prefrontal cortex