133,134 Figure 1. Neuroplasticity and cellular resilience in mood disorders. There are multiple influences on neuroplasticity and cellular resilience in mood disorders. Genetic/neurodevelopmental factors, repeated affective episodes, and illness progression may all contribute … In addition to regulating synaptic efficacy, BDNF appears to function as a modulator that, is required for the induction, expression, and/or maintenance of LTP. Thus, genetic deletion of BDNF in mice disrupts normal induction of LTP, which can be rescued by reintroducing

BDNF either by transfecting hippocampal Inhibitors,research,lifescience,medical slices with BDNF-expressing adenovirus or the exogenous administration of BDNF.127

Inhibitors,research,lifescience,medical The information reviewed here clearly shows that neurotrophin selleck chemical signaling cascades play a major role in regulating various forms of neuronal and synaptic plasticity, as well as neuronal survival – all of which may be impaired in severe recurrent mood disorders. We now turn to a. discussion of the evidence that neurotrophic signaling cascades are long-term targets for antidepressants and mood stabilizers. Influence of antidepressant treatment on cell survival pathways In an extensive series of studies, Inhibitors,research,lifescience,medical Duman and associates have demonstrated that the cyclic adenosine monophosphate (cAMP)-cAMP response element, binding protein (CRHB) cascade – an important pathway involved Inhibitors,research,lifescience,medical in cell survival and plasticity – is upregulated by chronic antidepressant treatment, in a timeframe that parallels clinical response.7,135-138 The results include increased coupling of the stimulatory G-protein, Gs, to adenylyl cyclase, increased protein kinase A (PKA) activity in the particulate

fraction of limbic structures, increased PKA levels in the nuclear Inhibitors,research,lifescience,medical fractions of cerebral cortex, and increased mRNA expression of the type 1 adenylyl cyclase in the rat hippocampus.7,135 Sclareol The same workers have found that chronic administration of different, classes of antidepressants – SSRIs (fluoxetine and sertraline), a selective norepinephrine reuptake inhibitor (desipramine), a dual aminergic reuptake inhibitor (imipramine) – and chronic electroconvulsive seizures upregulate the expression of CREB.7,135 By contrast, the nonantidepressant psychotropic drugs cocaine and haloperidol, did not, influence CREB mRNA expression indicating the specificity of CREB induction to antidepressants. Chronic administration of these antidepressants has also been demonstrated to increase mRNA and protein levels of the cAMP-specific phosphodiesterase PDE4 isozymes, PDE4A and PDE4B, in rat frontal cortex (FC) and hippocampus.