title: 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.
authors.affiliation: Institute of Cytology and Genetics, Novosibirsk, Russia. dygalo@bionet.nsc.ru
authors.forename: Nikolay N
authors.initials: NN
authors.lastname: Dygalo
authors.forename: Tatyana S
authors.initials: TS
authors.lastname: Kalinina
authors.forename: Veta V
authors.initials: VV
authors.lastname: Bulygina
authors.forename: Galina T
authors.initials: GT
authors.lastname: Shishkina
mesh_terms: D000818:Animals; D017209:Apoptosis; D001519:Behavior; D001921:Brain / Q000378:metabolism* / Q000473:pathology*; D003863:Depression / Q000188:drug therapy / Q000209:etiology*; D006801:Humans; D055500:Resilience, Psychological; D013315:Stress, Psychological / Q000150:complications*; D051020:bcl-X Protein / Q000378:metabolism*
chemical_list: D051020:bcl-X Protein