Chronic alcohol abuse is implicated in the oxidative stress and the changes in the neurotrophic factor receptor expression in the human CNS

Abstract

Alcohol abuse and alcoholism induce brain damage, and, in some cases, neurodegeneration. The pathogenesis of the alcohol-induced injury of the CNS is a complex process in which oxidative stress plays an essential role. Alcohol increases the formation of reactive oxygen species and affects the antioxidant defense system of the brain. It is well known that oxidative stress induces apoptosis in neurons, as well as in other cell types. Neurotropins and their receptors have a crucial role in neural regulation. The aim of this study is an overall analysis of the CNS neuronal and glial cell death and the oxidative status by the use of immunohistochemical methods. Three different CNS regions – cortical, subventricular and basal ganglia were analyzed in the autopsy samples obtained from 10 chronic alcohol abused patients. The immunohistochemical detection of oxidative damage was performed using anti-Cu/Zn SOD monoclonal antibody, neural activity – anti-NGFR (p75^NTR) antibody, apoptosis – the TUNEL reaction. Both, quantitative and semiquantitative estimations were used for the evaluation of results. The subventricular zone was characterized by a negative (75%) and a moderate (25%) astroglial SOD1 expression, the basal ganglia region – by strong (43%), moderate (43%), and low (14%) neuronal and moderate (71%) and low (29%) astroglial SOD1 expression, whereas, the cortex – by strong (33%) and moderate (66%) neuronal and moderate (67%), low (17%) and negative (17%) astroglial expression. The SOD1 expression was not detected in oligodendroglia and ependymocytes. Brain regions showed variability in the apoptotic cell death rates. Neuronal TUNEL-positive staining in basal ganglia was higher than in the cerebral cortex. TUNEL-positive astrocytes were detected in the white matter, more frequently in the basal ganglia region when compared to the cortex. The apoptosis marker was nearly absent in ependymal and oligodendroglial cells. The rate of TUNEL-positive cortex endothelial cells was detected at 7.9% level in the case of chronic alcohol abuse. Neuronal processes showed heterogeneous NGFR expression: in the cortex, basal ganglia and the subventricular zone (negative/low), whereas the subcortex and the white matter – moderate and moderate/strong, accordingly. Alcohol-induced CNS vulnerability is related to the increase in oxidative stress; furthermore, it suggests an increased risk of neurodegeneration for neuronal and glial cells.