Embodiment of an Emotional State Concurs with a Stress-Induced Reconsolidation Impairment Effect on an Auditory Verbal Word-List Memory.

Stress alters memory. Understanding how and when acute stress improves or impairs memory is a challenge. Stressors can affect memory depending on a combination of factors. Typically, mild stressors and stress hormones might promote consolidation of memory processing and impair memory retrieval. However, studies have shown that during reconsolidation, stressors may either enhance or impair recalled memory. We propose that a function of reconsolidation is to induce changes in the behavioral expression of memory. Here, we adapted the Rey Auditory Verbal Learning Test (RAVLT) to evaluate the effect of cold pressor stress (CPS) during the reconsolidation of this declarative memory. A decay in memory performance attributable to forgetting was found at the time of memory reactivation 5 d after training (day 6). Contrary to our initial predictions, the administration of CPS after memory reactivation impaired long-term memory expression (day 7), an effect dependent on the presence of a mismatch during Reactivation Session. No differences in recognition tests were found. To assess putative sources of the negative memory modulation effects induced during reconsolidation, current emotional state was evaluated immediately after Testing Session (day 7). An increase in arousal was revealed only when CPS was administered concurrently with memory reactivation-labilization. The possibility of integration during reconsolidation of independent associations of these emotive components in the trace is a critical factor in modulating neutral memories during reconsolidation by stressors.

The levels of RAC3 expression are up regulated by TNF in the inflammatory response.

RAC3 is a coactivator of glucocorticoid receptor and nuclear factor-κB (NF-κB) that is usually over-expressed in tumors and which also has important functions in the immune system. We investigated the role of the inflammatory response in the control of RAC3 expression levels in vivo and in vitro. We found that inflammation regulates RAC3 levels. In mice, sub-lethal doses of lipopolysaccharide induce the increase of RAC3 in spleen and the administration of the synthetic anti-inflammatory glucocorticoid dexamethasone has a similar effect. However, the simultaneous treatment with both stimuli is mutually antagonistic. In vitro stimulation of the HEK293 cell line with tumor necrosis factor (TNF), one of the cytokines induced by lipopolysaccharide, also increases the levels of RAC3 mRNA and protein, which correlates with an enhanced transcription dependent on the RAC3 gene promoter. We found that binding of the transcription factor NF-κB to the RAC3 gene promoter could be responsible for these effects. Our results suggest that increase of RAC3 during the inflammatory response could be a molecular mechanism involved in the control of sensitivity to both pro- and anti-inflammatory stimuli in order to maintain the normal healthy course of the immune response.

Nuclear receptor coactivator RAC3 inhibits autophagy.

RAC3 is an oncogene naturally overexpressed in several tumors. Besides its role as coactivator, it can exert several protumoral cytoplasmic actions. Autophagy was found to act either as a tumor suppressor during the early stages of tumor development, or as a protector of the tumor cell in later stages under hypoxic conditions. We found that RAC3 overexpression inhibits autophagy when induced by starvation or rapamycin and involves RAC3 nuclear translocation-dependent and -independent mechanisms. Moreover, hypoxia inhibits the RAC3 gene expression leading to the autophagy process, allowing tumor cells to survive until angiogenesis occurs. The interplay between RAC3, hypoxia, and autophagy could be an important mechanism for tumor progression and a good target for a future anticancer therapy.