Considerable evidence indicates that glucocorticoid hormones enhance the consolidation of long-term memories for emotionally arousing experiences but not that for less arousing or neutral information. However, previous studies have not determined the basis of such arousal-induced selectivity. Here we report the finding that endogenous noradrenergic activation of the basolateral complex of the amygdala (BLA) induced by emotional arousal is essential in enabling glucocorticoid memory enhancement. Corticosterone administered immediately after object recognition training enhanced 24-h memory of naïve male rats but not that of rats previously habituated to the training context in order to reduce novelty-induced emotional arousal. The ␤-adrenoceptor antagonist propranolol administered either systemically or into the BLA blocked the corticosterone-induced memory enhancement. Further, in habituated rats, corticosterone activated BLA neurons, as assessed by phosphorylated cAMP response element binding (pCREB) immunoreactivity levels, and enhanced memory only when norepinephrine release was stimulated by administration of the ␣2-adrenoceptor antagonist yohimbine. These findings strongly suggest that synergistic actions of glucocorticoids and emotional arousal-induced noradrenergic activation of the BLA constitute a neural mechanism by which glucocorticoids may selectively enhance memory consolidation for emotionally arousing experiences.corticosterone ͉ emotional arousal ͉ norepinephrine ͉ object recognition ͉ memory consolidation E xtensive evidence indicates that emotionally arousing experiences are typically well remembered (1, 2). Investigations of the underlying neurobiological mechanisms suggest that glucocorticoids, released from the adrenal cortex by emotional arousal, play a key role in the strengthening of new memory traces (3-5). Recent findings of both animal and human studies suggest that glucocorticoids may selectively modulate the consolidation of memories of emotionally arousing stimuli (6-9) or those of experiences occurring during states of emotional arousal (10). Such findings imply that glucocorticoids interact with some other component of emotional arousal in influencing memory consolidation. We reported evidence that selective blockade of noradrenergic activity in the basolateral complex of the amygdala (BLA) of rats with infusions of a ␤-adrenoceptor antagonist prevented the memory-enhancing effects of glucocorticoids administered either systemically or into selected brain regions (11-13). Such findings, considered along with the evidence that emotional arousal activates the BLA (14-19) and induces the release of norepinephrine within the BLA (20, 21), suggest that emotional arousal-induced noradrenergic activation within the BLA may be essential in enabling glucocorticoid effects on memory consolidation. However, because prior experiments investigating glucocorticoid-noradrenergic interactions on memory consolidation have used training conditions that induce the release of high levels of norepineph...

Gram-negative bacteria contain a double-membrane cellular envelope that enables them to colonize harsh environments and prevents entry of many clinically available antibiotics. A main component of most outer membranes is lipopolysaccharide (LPS), a glycolipid containing multiple fatty acyl chains and up to hundreds of sugars that is synthesized in the cytoplasm. In the last two decades, the proteins responsible for transporting LPS across the cellular envelope and assembling it at the cell surface in Escherichia coli have been identified, but it remains unclear how they function. In this Review, we discuss recent advances in this area and present a model explaining how energy from the cytoplasm is used to power LPS transport across the cellular envelope to the cell surface.

3‐Hydroxykynurenine (3‐HK) is a potential endogenous neurotoxin whose increased levels have been described in several neurodegenerative disorders. Here, we characterized in vitro neurotoxicity of 3‐HK. Of the tested kynurenine pathway metabolites, only 3‐HK, and to a lesser extent 3‐hydroxyanthranilic acid, were toxic to primary cultured striatal neurons. 3‐HK toxicity was inhibited by various antioxidants, indicating that the generation of reactive oxygen species is essential to the toxicity. 3‐HK‐induced neuronal cell death showed several features of apoptosis, as determined by the blockade by macromolecule synthesis inhibitors, and by the observation of cell body shrinkage with nuclear chromatin condensation and fragmentation. In addition, 3‐HK toxicity was dependent on its cellular uptake via transporters for large neutral amino acids, because uptake inhibition blocked the toxicity. Cortical and striatal neurons were much more vulnerable to 3‐HK toxicity than cerebellar neurons, which may be attributable to the differences in transporter activities of these neurons. These results indicate that 3‐HK, depending on transporter‐mediated cellular uptake and on intracellular generation of oxidative stress, induces neuronal cell death with brain region selectivity and with apoptotic features, which may be relevant to pathology of neurodegenerative disorders.

Considerable evidence implicates glucocorticoid hormones in the regulation of memory consolidation and memory retrieval. The present experiments investigated whether the influence of these hormones on memory depends on the level of emotional arousal induced by the training experience. We investigated this issue in male Sprague-Dawley rats by examining the effects of immediate posttraining systemic injections of the glucocorticoid corticosterone on object recognition memory under two conditions that differed in their training-associated emotional arousal. In rats that were not previously habituated to the experimental context, corticosterone (0.3, 1.0, or 3.0 mg͞kg, s.c.) administered immediately after a 3-min training trial enhanced 24-hr retention performance in an inverted-U shaped dose-response relationship. In contrast, corticosterone did not affect 24-hr retention of rats that received extensive prior habituation to the experimental context and, thus, had decreased novelty-induced emotional arousal during training. Additionally, immediate posttraining administration of corticosterone to nonhabituated rats, in doses that enhanced 24-hr retention, impaired object recognition performance at a 1-hr retention interval whereas corticosterone administered after training to well-habituated rats did not impair 1-hr retention. Thus, the present findings suggest that training-induced emotional arousal may be essential for glucocorticoid effects on object recognition memory.corticosterone ͉ stress hormones ͉ memory consolidation ͉ memory retrieval

Bacterial lipoproteins are synthesized as precursors in the cytoplasm and processed into mature forms on the cytoplasmic membrane. A lipid moiety attached to the N terminus anchors these proteins to the membrane surface. Many bacteria are predicted to express more than 100 lipoproteins, which play diverse functions on the cell surface. The Lol system, composed of five proteins, catalyzes the localization of Escherichia coli lipoproteins to the outer membrane. Some lipoproteins play vital roles in the sorting of other lipoproteins, lipopolysaccharides, and β-barrel proteins to the outer membrane. On the basis of results from biochemical, genetic, and structural studies, we discuss the biogenesis of lipoproteins in bacteria, their importance in cellular functions, and the molecular mechanisms underlying efficient sorting of hydrophobic lipoproteins to the outer membrane through the hydrophilic periplasm.