Phenotypic variability of cerebral neurons reaction. Chronic action of toxins at high and low sensitivity to them

To evaluate the influence of chronic ethanol intoxication and bacterial lipopolysaccharide on the phenotype of the neurons and their environment a pilot study in the two series was conducted using 25 rats with different initial sensitivity to these toxins. The regions of the frontal cortex, striatum, anterior hypothalamus, cerebellar cortex, and medulla oblongata were investigated. To assess toxin action we used such morphometric parameters as the average degree of neuron damage, the ratio glia/neuron, the expression of neuronal and endothelial nitroxide synthesis, and proapoptotic ligand TRAIL. Experimental chronic intoxication caused the similar changes in the neurons of studied brain areas, which were maximally expressed in the frontal cortex and the anterior hypothalamic nuclei. The constitutional high sensitivity to toxins predetermined more intensive changes of neurons, the reactions of glial cells, and vascular endothelium in these areas in comparison to the subgroups. A relatively high expression of endothelial nitroxide synthase and TRAIL was a character trait for animals with high sensitivity to toxins. The presented data indicate the presence of molecular predictors for neuronal sensitivity to chronic toxic effects, including those associated with the mechanisms of neuroglial relationships, balance between nitroxide syntheses, and control apoptosis of neurons. They, of course, determine the final sensitivity to exogenous neurotropic toxic effects, the amount of which is determined by the specifics of the current toxic agent and type of animal.