Vesicular signalling and immune modulation as hedonic fingerprints: proteomic profiling in the chronic mild stress depression model.

Extensive preclinical research has focused at unravelling the underlying molecular mechanisms leading to depression and recovery. In this study, we investigated the quantitative changes in protein abundance in the ventral hippocampal granular cell layer. We compared different phenotypes from the chronic mild stress (CMS) model of depression using chronic administration with two selective serotonin reuptake inhibitors (SSRIs), escitalopram and sertraline.

The number of granule cells in rat hippocampus is reduced after chronic mild stress and re-established after chronic escitalopram treatment.

Stress and depression cause structural changes in the hippocampal formation. Some of these can be reversed by chronic antidepressant treatment. In the present study, we examined the changes in the total number of granule cells and the volume of the granule cell layer after exposing rats to chronic mild stress and chronic escitalopram treatment.

Proteomic investigation of the ventral rat hippocampus links DRP-2 to escitalopram treatment resistance and SNAP to stress resilience in the chronic mild stress model of depression.

The development of depression as well as recovery from depression is most likely accompanied by a change in protein expression profiles. The purpose of the present study was to quantitatively investigate global protein expression differences independent of any hypothesis describing depression etiology and recovery. Thus two-dimensional differential in-gel electrophoresis was employed to compare the ventral hippocampal proteomes between different treatment groups in the chronic mild stress (CMS) model of depression.

Serotonin(4) (5-HT(4)) receptor agonists are putative antidepressants with a rapid onset of action.

Current antidepressants are clinically effective only after several weeks of administration. Here, we show that serotonin(4) (5-HT(4)) agonists reduce immobility in the forced swimming test, displaying an antidepressant potential. Moreover, a 3 day regimen with such compounds modifies rat brain parameters considered to be key markers of antidepressant action, but that are observed only after 2-3 week treatments with classical molecules: desensitization of 5-HT(1A) autoreceptors, increased tonus on hippocampal postsynaptic 5-HT(1A) receptors, and enhanced phosphorylation of the CREB protein and neurogenesis in the hippocampus.

Hippocampal cytogenesis correlates to escitalopram-mediated recovery in a chronic mild stress rat model of depression.

From clinical studies it is known that recurrent depressive episodes associate with a reduced hippocampal volume. Conversely, preclinical studies have shown that chronic antidepressant treatment increases hippocampal neurogenesis. Consequently, it has been suggested that a deficit in hippocampal neurogenesis is implicated in the pathophysiology of depression.