Increased Expression of the Anti-Apoptotic Protein Bcl-xL in the Brain is Associated with Resilience to Stress-Induced Depression-Like Behavior

Abstract

Clinical observations and the results of animal studies have implicated changes in neuronal survival and plasticity in both the etiology of mood disorders, especially stress-induced depression, and anti-depressant drug action. Stress may predispose individuals toward depression through down-regulation of neurogenesis and an increase in apoptosis in the brain. Substantial individual differences in vulnerability to stress are evident in humans and were found in experimental animals. Recent studies revealed an association between the brain anti-apoptotic protein B cell lymphoma like X, long variant (Bcl-xL) expression and individual differences in behavioral vulnerability to stress. The ability to increase Bcl-xL gene expression in the hippocampus in response to stress may be an important factor for determining the resistance to the development of stress-induced depression. Treatment with anti-depressant drugs may change Bcl-xL response properties. In the rat brainstem, expression of this anti-apoptotic gene becomes sensitive to swim stress during the long-term fluoxetine treatment, an effect that appeared concomitantly with the anti-depressant-like action of the drug in the forced swim test, suggesting that Bcl-xL may be a new target for depression therapy. The processes and pathways linking stress stimuli to behavior via intracellular anti-apoptotic protein are discussed here in the context of Bcl-xL functions in the mechanisms of individual differences in behavioral resilience to stress and anti-depressant-induced effects on the behavioral despair.

Dietary EPA‐Enriched Phospholipids Alleviate Chronic Stress and LPS‐Induced Depression‐ and Anxiety‐Like Behavior by Regulating Immunity and Neuroinflammation

“…[34] Apoptosis is the main mechanism underlying neuronal loss, which in turn exacerbates GR-mediated HPA disorder and monoamine system dysfunction. [51,52] In the present study, dietary EPA-PL and EPA-EE inhibited the apoptosis by mitochondria-mediated apoptotic (Bax/Bcl-2-caspase-9/3) pathway, and EPA-PL showed excellent effects. It has been reported that EPA-EE significantly reduced www.advancedsciencenews.com www.mnf-journal.com Figure 8.…”

Rodent Models of Depression: Neurotrophic and Neuroinflammatory Biomarkers

“…In addition, different rodent strains used, different maintaining conditions, and obvious gender dependence of the stress response make a large portion of the published data contradictory and fragmentary. Taking this into account, a future perspective of using stress-related models of depression may be related to investigations of mechanisms contributing to individual differences in vulnerability to stress-induced depression [143, 201, 202] as well as of the impact of parent's exposure to stress on individual's risk for clinical depression in offspring [203]. Models of interoceptive stress (including proinflammatory stressor, particularly systemic LPS administration), though much further from the etiological “human” stressors, seem potentially more “unifiable.” If the goal is to investigate the involvement of NTFs and cytokines in the development of depression-like syndromes, these models deserve more attention and systematic studies.…”

Anti-Apoptotic Protein Bcl-xL Expression in the Midbrain Raphe Region Is Sensitive to Stress and Glucocorticoids

“…Important observations were also made using three genetically modified mouse models, all characterized by altered behaviors in depression-related paradigms, but demonstrated qualitative differences (significant decreases or increases) in tph2 mRNA expression in the DRN [ 72 ]. It is therefore clear that the suggested relationship between TPH and depression may be rather indirect and may depend, for example, on different neurotransmitter systems [ 69 ], hippocampal neurogenesis [ 73 ] as well as on cell survival factors [ 74 , 75 ].…”