Features of the Responses of the Protective Systems of the Brain in Adult Rats to Stressors and Lipopolysaccharide

Abstract

Susceptibility and resistance to depression is determined by the actions of the stimuli provoking it, including stressors and inflammatory processes, as well as the activity of the body’s protective systems, such as neurotrophins and antiapoptotic proteins. To clarify the effects of stressor and proinflammatory actions inducing a depression-like state on these protective mechanisms, we studied the role of the level of mRNA for brain-derived neurotrophic factor (BDNF) and antiapoptotic protein Bcl-xL in parts of the brain in adult male rats after 14 days of stressor (forced swimming or restricted mobility) or proinflammatory (administration of lipopolysaccharide, LPS) treatments. Both stressors significantly decreased BDNF expression in the midbrain; the decrease in neurotrophin expression in the cortex was significant after swimming but at the level of a tendency after restriction of mobility. After LPS, the level of BDNF mRNA decreased significantly in the hippocampus, but not in the midbrain – the areas in which stressors have influences. Both stressors increased Bcl-xL mRNA levels in the brainstem but produced reductions in the midbrain, with no change in other areas. LPS had no effect on Bcl-xL expression in most areas but decreased it in the brainstem, where the level of this transcript correlated negatively with the adrenal index. Overall, stressor and proinflammatory treatments induced changes in Bcl-xL expression unique to each treatment and even in opposite directions (in the brainstem). The prodepressive actions of both LPS and stressors were associated with decreases in BDNF expression located in brain areas specific for each treatment: in the hippocampus in the case of LPS and in the midbrain and prefrontal cortex in the case of stressors. These features of the responses of BDNF and Bcl-xL point to significant differences in the pathways of induction of psychoemotional pathology by stress and activation of inflammation.