Glial and glutamatergic markers in depression, alcoholism, and their comorbidity

• Published in: Journal of affective disorders Vol. 127; no. 1; pp. 230 - 240
• Main Authors: Miguel-Hidalgo, José Javier, Waltzer, Robert, Whittom, Angela A., Austin, Mark C., Rajkowska, Grazyna, Stockmeier, Craig A.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier B.V 01.12.2010; Elsevier
• Subjects: Addictive behaviors; Adult; Adult and adolescent clinical studies; Aged; Alcohol dependence; Alcoholics; Alcoholism; Alcoholism - epidemiology; Alcoholism - pathology; Alcoholism - physiopathology; Alcoholism and acute alcohol poisoning; Astrocytes; Astrocytes - pathology; Astrocytes - physiology; Biological and medical sciences; Comorbidity; Depression; Depressive Disorder, Major - epidemiology; Depressive Disorder, Major - pathology; Depressive Disorder, Major - physiopathology; Depressive personality disorders; Excitatory Amino Acid Transporter 1 - metabolism; Excitatory Amino Acid Transporter 2; Female; Frontal Lobe - pathology; Frontal Lobe - physiopathology; Glial Fibrillary Acidic Protein - metabolism; Glutamate Plasma Membrane Transport Proteins - metabolism; Glutamate-Ammonia Ligase - metabolism; Glutamine - physiology; Human; Humans; Major depressive disorder; Male; Medical sciences; Middle Aged; Mood disorders; Orbitofrontal cortex; Postmortem; Prefrontal Cortex - pathology; Prefrontal Cortex - physiopathology; Proteins; Psychiatric/Mental Health; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Reference Values; Synaptic Transmission - physiology; Toxicology; Human; Alcohol dependence; Orbitofrontal cortex; Astrocytes; Major depressive disorder; Postmortem; Mood disorder; Neuroglia; Alcoholism; Central nervous system; Depression; Astrocyte; Encephalon; Alcoholic beverage; Concomitant disease; Dependence
• ISSN: 0165-0327; 1573-2517; 1573-2517
• DOI: 10.1016/j.jad.2010.06.003

Alteration of glutamatergic neurotransmission in the prefrontal cortex (PFC) may contribute to the pathophysiology of alcoholism and major depressive disorder (MDD). Among glial cells, astrocytes are mostly responsible for recycling synaptic glutamate by uptake through excitatory amino acid transporters 1 and 2 (EAAT1 and EAAT2), and conversion to glutamine with glutamine synthetase (GS). Low density of astrocytes in the PFC of “uncomplicated’ alcoholics and MDD subjects may parallel altered glutamate transporters and GS in the PFC. Immunohistochemistry and Western blotting for glutamate transporters, GS and glial fibrillary acidic protein (GFAP) were applied to postmortem tissue of the left orbitofrontal cortex from 13 subjects with MDD, 13 with alcoholism, 10 with comorbid alcoholism plus MDD (MDA), and 13 non-psychiatric controls. Area fraction of immunoreactivity was measured in sections, and protein levels in Western blots. EAAT2 immunoreactivity was significantly lower in MDD and MDA subjects than in controls. EAAT1 levels were lower in MDA and MDD subjects as compared to controls, while GS levels in MDA were significantly lower than in alcoholics and controls, and lower in MDD subjects than in alcoholics. Area fraction of GFAP was lower in MDD, but not in MDA subjects as compared to controls or alcoholics. High variability of protein levels in some groups and effects of antidepressant treatment, although appearing to be limited, cannot be fully evaluated. There are differential changes in the expression of glial glutamatergic markers in depression and alcoholism, suggesting a depletion of certain aspects of glutamatergic processing in depression.