Comparison of prefrontal cell pathology between depression and alcohol dependence

Abstract

Chronic alcohol abuse is often co-morbid with depression symptoms and in many cases it appears to induce major depressive disorder. Structural and functional neuroimaging has provided evidence supporting some degree of neuropathological convergence of alcoholism and mood disorders. In order to understand the cellular neuropathology of alcohol dependence and mood disorders, postmortem morphometric studies have tested the possibility of alterations in the number and size of cells in the prefrontal cortex and other brain regions. The present review compares the cell pathology in the prefrontal cortex between alcohol dependence and depression, and reveals both similarities and differences. One of the most striking similarities is that, although pathology affects both neuronal and glial cells, effects on glia are more dramatic than on neurons in both alcohol dependence comorbid with depression and idiopathic depression. Moreover, prefrontal cortical regions are commonly affected in both depression and alcoholism. However, the cellular changes are more prominent and spread across cortical layers in alcohol dependent subjects than in subjects with mood disorders, and changes in glial nucleus size are opposite in alcoholism and depression. It could be argued that one defining factor in the manifestation of the depressive pathology is a reduction in the glial distribution in the dlPFC that is reflected in a reduced glial density. In alcoholism reduced glial nuclear size might be related to the cytotoxic effects of prolonged alcohol exposure, while in MDD, in the absence of alcohol abuse, other processes might be responsible for the increase in average size of glial nuclei. In either case abnormal function related to glial reduction would be associated with depression due to insufficient glial support to the surrounding neurons.

Markers of Apoptosis Induction and Proliferation in the Orbitofrontal Cortex in Alcohol Dependence

“…An early deficit in glial support combined with the functional alterations caused by alcohol exposure itself may result in progressively increased vulnerability of cortical neurons, although this hypothesis needs to be properly supported with further experiments. Since we did not determine the cell types where increased expression of C8 occurred, it was not possible to ascertain whether glial cells, neurons or both were responsible for the increased C8 or whether changes of C8 in glial cells preceded changes in neurons (Miguel-Hidalgo et al, 2006, Miguel-Hidalgo and Rajkowska, 2003). …”

Morphometric post-mortem studies in bipolar disorder: possible association with oxidative stress and apoptosis

“…Another confounding factor that needs to be clarified in future research is the influence of previous use of alcohol. Neurotoxic effects of alcohol are well known and some morphometric studies have shown alterations in glia and neurons in brains of alcoholics (Hercher et al 2009 ;Miguel-Hidalgo et al 2002 ;Miguel-Hidalgo & Rajkowska, 2003). Unfortunately, many brains collected for neuropathology studies have undergone alcohol abuse.…”

Blockade of Astrocytic Glutamate Uptake in the Prefrontal Cortex Induces Anhedonia

“…Decreases in PFC volume have been attributed to reductions in glial cells (Cotter et al, 2002;Hercher et al, 2009;Ongur et al, 1998;Rajkowska, 2000;Rajkowska et al, 1999) and to a lesser extent, neuronal atrophy (Cotter et al, 2002;Law and Harrison, 2003;Rajkowska, 2000;Rajkowska et al, 1999). Glial cell deficits in MDD are accompanied by a decrease in astrocytic markers in the PFC such as glial fibrillary acidic protein (Miguel-Hidalgo et al, 2000;Si et al, 2004) and glutamine synthetase (Choudary et al, 2005;Sequeira et al, 2009;Yildiz-Yesiloglu and Ankerst, 2006), as well as morphological changes including swelling of the size and shape of astrocytes (Miguel-Hidalgo and Rajkowska, 2003). Furthermore, downregulation in the high-affinity astrocytic glutamate transporters, SLC1A2 (EAAT2) and SLC1A3 (EAAT1), have been identified in prefrontal cortical areas of human post-mortem tissue; abnormalities that contribute to elevated glutamate levels in the PFC (Choudary et al, 2005).…”