The Grueneberg ganglion controls odor-driven food choices in mice under threat.

The ability to efficiently search for food is fundamental for animal survival. Olfactory messages are used to find food while being aware of the impending risk of predation. How these different olfactory clues are combined to optimize decision-making concerning food selection remains elusive. Here, we find that chemical danger cues drive the food selection in mice via the activation of a specific olfactory subsystem, the Grueneberg ganglion (GG). We show that a functional GG is required to decipher the threatening quality of an unfamiliar food. We also find that the increase in corticosterone, which is GG-dependent, enhances safe food preference acquired during social transmission. Moreover, we demonstrate that memory retrieval for food preference can be extinguished by activation of the GG circuitry. Our findings reveal a key function played by the GG in controlling contextual food responses and illustrate how mammalian organisms integrate environmental chemical stress to optimize decision-making

Effectiveness of ready-to-use therapeutic food compared to a corn/soy-blend-based pre-mix for the treatment of childhood moderate acute malnutrition in Niger.

Standard nutritional treatment of moderate acute malnutrition (MAM) relies on fortified blended flours though their importance to treat this condition is a matter of discussion. With the newly introduced World Health Organization growth standards, more children at an early stage of malnutrition will be treated following the dietary protocols as for severe acute malnutrition, including ready-to-use therapeutic food (RUTF). We compared the effectiveness of RUTF and a corn/soy-blend (CSB)-based pre-mix for the treatment of MAM in the supplementary feeding programmes (SFPs) supported by Médecins Sans Frontières, located in the Zinder region (south of Niger). Children measuring 65 to <110 cm, newly admitted with MAM [weight-for-height (WHM%) between 70% and <80% of the NCHS median] were randomly allocated to receive either RUTF (Plumpy'Nut®, 1000 kcal day(-1)) or a CSB pre-mix (1231 kcal day(-1)). Other interventions were similar in both groups (e.g. weekly family ration and ration at discharge). Children were followed weekly up to recovery (WHM% ≥ 85% for 2 consecutive weeks). In total, 215 children were recruited in the RUTF group and 236 children in the CSB pre-mix group with an overall recovery rate of 79.1 and 64.4%, respectively (p < 0.001). There was no evidence for a difference between death, defaulter and non-responder rates. More transfers to the inpatient Therapeutic Feeding Centre (I-TFC) were observed in the CSB pre-mix group (19.1%) compared to the RUTF group (9.3%) (p = 0.003). The average weight gain up to discharge was 1.08 g kg(-1) day(-1) higher in the RUTF group [95% confidence interval: 0.46-1.70] and the length of stay was 2 weeks shorter in the RUTF group (p < 0.001). For the treatment of childhood MAM in Niger, RUTF resulted in a higher weight gain, a higher recovery rate, a shorter length of stay and a lower transfer rate to the I-TFC compared to a CSB pre-mix. This might have important implications on the efficacy and the quality of SFPs

Food preference acquired by social transmission is altered by the absence of the olfactory marker protein in mice.

Food preference is conserved from the most primitive organisms to social animals including humans. A continuous integration of olfactory cues present both in food and in the different environmental and physiological contexts favors the intake of a given source of food or its avoidance. Remarkably, in mice, food preference can also be acquired by olfactory communication in-between conspecifics, a behavior known as the social transmission of food preference (STFP). STFP occurs when a mouse sniffs the breath of a conspecific who has previously eaten a novel food emitting specific odorants and will then develop a preference for this never encountered food. The efficient discrimination of odorants is performed by olfactory sensory neurons (OSNs). It is essential and supports many of the decision-making processes. Here, we found that the olfactory marker protein (OMP), an enigmatic protein ubiquitously expressed in all mature olfactory neurons, is involved in the fine regulation of OSNs basal activity that directly impacts the odorant discrimination ability. Using a previously described Omp null mouse model, we noticed that although odorants and their hedonic-associated values were still perceived by these mice, compensatory behaviors such as a higher number of sniffing events were displayed both in the discrimination of complex odorant signatures and in social-related contexts. As a consequence, we found that the ability to differentiate the olfactory messages carried by individuals such as those implicated in the social transmission of food preference were significantly compromised in Omp null mice. Thus, our results not only give new insights into the role of OMP in the fine discrimination of odorants but also reinforce the fundamental implication of a functional olfactory system for food decision-making

Odorant-Dependent Generation of Nitric Oxide in Mammalian Olfactory Sensory Neurons

The gaseous signalling molecule nitric oxide (NO) is involved in various physiological processes including regulation of blood pressure, immunocytotoxicity and neurotransmission. In the mammalian olfactory bulb (OB), NO plays a role in the formation of olfactory memory evoked by pheromones as well as conventional odorants. While NO generated by the neuronal isoform of NO synthase (nNOS) regulates neurogenesis in the olfactory epithelium, NO has not been implicated in olfactory signal transduction. We now show the expression and function of the endothelial isoform of NO synthase (eNOS) in mature olfactory sensory neurons (OSNs) of adult mice. Using NO-sensitive micro electrodes, we show that stimulation liberates NO from isolated wild-type OSNs, but not from OSNs of eNOS deficient mice. Integrated electrophysiological recordings (electro-olfactograms or EOGs) from the olfactory epithelium of these mice show that NO plays a significant role in modulating adaptation. Evidence for the presence of eNOS in mature mammalian OSNs and its involvement in odorant adaptation implicates NO as an important new element involved in olfactory signal transduction. As a diffusible messenger, NO could also have additional functions related to cross adaptation, regeneration, and maintenance of MOE homeostasis

Biochemical properties of Paracoccus denitrificans FnrP:Reactions with molecular oxygen and nitric oxide

In Paracoccus denitrificans, three CRP/FNR family regulatory proteins, NarR, NnrR and FnrP, control the switch between aerobic and anaerobic (denitrification) respiration. FnrP is a [4Fe-4S] cluster containing homologue of the archetypal O2 sensor FNR from E. coli and accordingly regulates genes encoding aerobic and anaerobic respiratory enzymes in response to O2, and also NO, availability. Here we show that FnrP undergoes O2-driven [4Fe-4S] to [2Fe-2S] cluster conversion that involves up to 2 O2 per cluster, with significant oxidation of released cluster sulfide to sulfane observed at higher O2 concentrations. The rate of the cluster reaction was found to be ~6-fold lower than that of E. coli FNR, suggesting that FnrP can remain transcriptionally active under microaerobic conditions. This is consistent with a role for FnrP in activating expression of the high O2 affinity cytochrome c oxidase under microaerobic conditions. Cluster conversion resulted in dissociation of the transcriptionally active FnrP dimer into monomers. Therefore, along with E. coli FNR, FnrP belongs to the subset of FNR proteins in which cluster type is correlated with association state. Interestingly, two key charged residues, Arg140 and Asp154, that have been shown to play key roles in the monomer-dimer equilibrium in E. coli FNR are not conserved in FnrP, indicating that different protomer interactions are important for this equilibrium. Finally, the FnrP [4Fe-4S] cluster is shown to undergo reaction with multiple NO molecules, resulting in iron nitrosyl species and dissociation into monomers

Application of 4,5-diaminofluorescein to reliably measure nitric oxide released from endothelial cells in vitro

Here we describe in more depth the previously published application of the fluorescent probe 4,5-diaminofluorescein (DAF-2) in order to reliably measure low levels of nitric oxide (NO) as released from human endothelial cells in vitro. The used approach is based on the following considerations a) use low concentrations of DAF-2 (0.1 µM) in order to reduce the contribution of DAF-2 auto-fluorescence to the measured total fluorescence, and b) subtract the DAF-2 auto-fluorescence from the measured total fluorescence. The advantage of this method is the reliable quantification of NO in a biological system in the nanomolar range once thoroughly validated. Here we focus in addition to the previous publication (Leikert et al., FEBS Lett 2001, 506:131-134) on aspects of validation procedures as well as limitations and pitfalls of this method

Breath Formate Is a Marker of Airway S-Nitrosothiol Depletion in Severe Asthma

-nitrosothiols (SNOs), a class of endogenous airway smooth muscle relaxants. This deficiency results from increased activity of an enzyme that both reduces SNOs to ammonia and oxidizes formaldehyde to formic acid, a volatile carboxylic acid that is more easily detected in exhaled breath condensate (EBC) than SNOs. We therefore hypothesize that depletion of airway SNOs is related to asthma pathology, and breath formate concentration may be a proxy measure of SNO catabolism. (r = −0.39, p = 0.002, asthmatics only), and positively correlated with the NO-derived ion nitrite (r = 0.46, p<0.0001) as well as with total serum IgE (r = 0.28, p = 0.016, asthmatics only). Furthermore, formate was not significantly correlated with other volatile organic acids nor with inhaled corticosteroid dose.-nitrosothiols

Enhanced Astrocytic Nitric Oxide Production and Neuronal Modifications in the Neocortex of a NOS2 Mutant Mouse

BACKGROUND: It has been well accepted that glial cells in the central nervous system (CNS) produce nitric oxide (NO) through the induction of a nitric oxide synthase isoform (NOS2) only in response to various insults. Recently we described rapid astroglial, NOS2-dependent, NO production in the neocortex of healthy mice on a time scale relevant to neuronal activity. To explore a possible role for astroglial NOS2 in normal brain function we investigated a NOS2 knockout mouse (B6;129P2-Nos2(tm1Lau)/J, Jackson Laboratory). Previous studies of this mouse strain revealed mainly altered immune responses, but no compensatory pathways and no CNS abnormalities have been reported. METHODOLOGY/PRINCIPAL FINDINGS: To our surprise, using NO imaging in brain slices in combination with biochemical methods we uncovered robust NO production by neocortical astrocytes of the NOS2 mutant. These findings indicate the existence of an alternative pathway that increases basal NOS activity. In addition, the astroglial mutation instigated modifications of neuronal attributes, shown by changes in the membrane properties of pyramidal neurons, and revealed in distinct behavioral abnormalities characterized by an increase in stress-related parameters. CONCLUSIONS/SIGNIFICANCE: The results strongly indicate the involvement of astrocytic-derived NO in modifying the activity of neuronal networks. In addition, the findings corroborate data linking NO signaling with stress-related behavior, and highlight the potential use of this genetic model for studies of stress-susceptibility. Lastly, our results beg re-examination of previous studies that used this mouse strain to examine the pathophysiology of brain insults, assuming lack of astrocytic nitrosative reaction