Modulation of the nuclear factor-kappa B (NF-κB) signalling pathway by glutamine in peritoneal macrophages of a murine model of protein malnutrition.

BACKGROUND AND AIMS: Protein malnutrition affects resistance to infection by impairing the inflammatory response, modifying the function of effector cells, such as macrophages. Recent studies have revealed that glutamine-a non-essential amino acid, which could become conditionally essential in some situations like trauma, infection, post-surgery and sepsis-is able to modulate the synthesis of cytokines. The aim of this study was to evaluate the effect of glutamine on the expression of proteins involved in the nuclear factor-kappa B (NF-κB) signalling pathway of peritoneal macrophages from malnourished mice. METHODS: Two-month-old male Balb/c mice were submitted to protein-energy malnutrition (n = 10) with a low-protein diet containing 2 % protein, whereas control mice (n = 10) were fed a 12 % protein-containing diet. The haemogram and analysis of plasma glutamine and corticosterone were evaluated. Peritoneal macrophages were pre-treated in vitro with glutamine (0, 0.6, 2 and 10 mmol/L) for 24 h and then stimulated with 1.25 µg LPS for 30 min, and the synthesis of TNF-α and IL-1α and the expression of proteins related to the NF-κB pathway were evaluated. RESULTS: Malnourished animals had anaemia, leucopoenia, lower plasma glutamine and increased corticosterone levels. TNF-α production of macrophages stimulated with LPS was significantly lower in cells from malnourished animals when cultivated in supraphysiological (2 and 10 mmol/L) concentrations of glutamine. Further, glutamine has a dose-dependent effect on the activation of macrophages, in both groups, when stimulated with LPS, inducing a decrease in TNF-α and IL-1α production and negatively modulating the NF-κB signalling pathway. CONCLUSIONS: These data lead us to infer that the protein malnutrition state interferes with the activation of macrophages and that higher glutamine concentrations, in vitro, have the capacity to act negatively in the NF-κB signalling pathway.

Arcopallium, NMDA antagonists and ingestive behaviors in pigeons.

This study investigated the effects of local injections of 6,7-dinitroquinoxaline-2,3(1H,4H)-dione (DNQX, AMPA-kainate receptor antagonist, 0.8 and 2.7 nmol) and MK-801 (NMDA receptor antagonist, 1.8 and 6.0 nmol) into the nucleus taeniae of the amygdala (TnA) and the arcopallium intermedium (AI) on ingestive and non-ingestive behaviors in free-feeding pigeons. Injections of DNQX into the TnA or into the AI failed to consistently affect feeding behavior; DNQX vehicle (DMSO) affected drinking when injected into the TnA. MK-801 injections into the AI produced a delayed increase in food and water intake. In the TnA, MK-801 increased water intake in the first two hours after the treatment. These data indicate that glutamatergic circuits in arcopallial structures in the pigeon, comparable to the mammalian medial amygdala, are involved in the inhibitory control of ingestive behaviors, suggesting that this can represent a conserved functional attribute in the amniote prosencephalon.

Tonic serotonergic control of ingestive behaviours in the pigeon (Columba livia): the role of the arcopallium.

This study examined the acute changes in feeding and drinking behaviours of free-feeding and free-drinking pigeons, in response to local injections of metergoline (MET, 5-HT(1/2) receptor antagonist; 7 and 20 nmol), GR46611 (GR, 5-HT(1B/1D) agonist; 2 and 6 nmol) or vehicle, into two components of the arcopallium: the nucleus taeniae of the amygdala (TnA) and the arcopallium intermedium (AI). In the TnA, the highest MET dose elicited a short-lived hyperphagy, without affecting drinking or non-ingestive behaviours during the first hour after injection. In contrast, all MET doses promptly increased drinking when injected in the AI, without affecting feeding; this effect was still evident 3 and 24 h after the treatment. When injected in the TnA, the highest GR dose promptly increased both food and water intake; these effects persisted 24 h after the treatments. GR injections in the AI evoked long-lasting increases in drinking, but not in feeding. Injections of these drugs into other arcopallial nuclei evoked no significant ingestive effects. These data indicate the presence of a tonic inhibitory influence of serotonergic inputs, partially mediated by 5-HT(1B/1D) receptors, on feeding- and drinking-related TnA circuits and on mechanisms controlling drinking in the AI. Compared to data from the rodent medial amygdala, our results suggest that a tonic inhibitory 5-HTergic control of feeding (but not drinking) behaviour, mediated by 5-HT(1/2) receptors and exerted in the medial amygdaloid area, may represent a broadly conserved functional attribute in the amniote brain, but probably involves many important taxa-specific neural mechanisms.

Ingestive effects of NMDA and AMPA-kainate receptor antagonists microinjections into the lateral hypothalamus of the pigeon (Columba livia).

This study examined the ingestive and behavioral effects of NMDA- and AMPA/kainate glutamatergic receptor blockade in the lateral hypothalamic area (LHy) of free-feeding pigeons (Columba livia). Injections of MK-801 (NMDA receptor antagonist; 6 nmol) or CNQX (AMPA/kainate receptor antagonist; 25.8 nmol) into the LHy of free-feeding pigeons induced significant increases in food intake and in feeding duration, as well as reductions in the latency to start feeding. Duration, latency and volume of water intake, as well as duration of sleep-like behavior, alert immobility, locomotion and preening were not changed by these treatments in the LHy. These results indicate that glutamatergic inputs to cells containing NMDA and/or AMPA receptors located in the LHy could modify both the beginning of a feeding bout (or the end of a period of satiety) and its duration (satiation). Our data also suggest that these inhibitory glutamatergic influences on feeding behavior are tonically active in the LHy.