The olfactory bulb (OB) has been recently identified as a circadian oscillator capable of operating independently of the master circadian pacemaker, the suprachiasmatic nuclei of the hypothalamus. OB oscillations manifest as rhythms in clock genes, electrical activity, and odor sensitivity. Dopamine, norepinephrine, and serotonin have been shown to modulate olfactory information processing by the OB and may be part of the mechanism that underlies diurnal changes in olfactory sensitivity. Rhythmic release of these neurotransmitters could generate OB rhythms in electrical activity and olfactory sensitivity. We hypothesized that these monoamines were rhythmically released in the OB. To test our hypotheses, we examined monoamine levels in the OB, over the course of a day, by high-performance liquid chromatography coupled to electrochemical detection. We observed that dopamine and its metabolite, DOPAC, rhythmically fluctuate over the day. In contrast, norepinephrine is arrhythmic. Serotonin and its metabolite HIAA appear to rhythmically fluctuate. Each of these monoamines has been shown to alter OB circuit behavior and influence odor processing. Rhythmic release of serotonin may be a mechanism by which the suprachiasmatic nuclei communicate, indirectly, with the OB.
The i.v. lipid emulsion (LIP) is a source of oxidants, which may stimulate inflammation. Coadministration of parenteral multivitamins (MVP) with LIP prevents lipid peroxidation in lightexposed total parenteral nutrition (TPN). We hypothesized that this modality of TPN administration affects systemic inflammation, which may be modulated by exposure to oxygen. Premature infants were allocated to three TPN regimens: control regimen -MVP coadministered with amino acid/dextrose exposed to ambient light, LIP provided separately (n ϭ 9) -LIPϩMVP light exposed (LE): MVP coadministered with light-exposed LIP (n ϭ 9) -LIPϩMVP light protected (LP): MVP coadministered with light-protected LIP (n ϭ 8). In LE and LP, amino acid/dextrose was provided separately. On reaching full TPN, infants were sampled for IL-6 and IL-8 in plasma and the redox potential of glutathione in whole blood (E, mV). Data were compared (ANOVA) in infants exposed to low (Ͻ0. S upplemental oxygen, assisted ventilation, and total parenteral nutrition (TPN) are therapies that expose premature infants to significant oxidant and inflammatory stress (1-4). As these infants are particularly deficient in antioxidant and anti-inflammatory defenses, such therapies may also have potentially harmful long-term effects on their developing lungs and brain (5).Synergistic deleterious effects of inflammation and oxidant stress in preterm infants can occur through a number of potential mechanisms. Exposure to oxygen leads to the accumulation of reactive oxygen species (ROS), which results in the generation of hydrogen and lipid peroxides. When antioxidant defenses are overwhelmed, this reaction self-propagates, and the peroxides generated can damage cells and tissues (6). In preterm infants, even brief periods of supplemental oxygen at birth may produce sufficient oxidant stress to cause sustained lung disease (7). Also, oxidized lipids and hydrogen peroxides have a direct modulatory effect on inflammatory pathways, including Toll-like receptors (8), and the transcriptional activator nuclear factor (NF)-kB (9). Such a direct activation of inflammatory pathways by oxygen byproducts can potentiate inflammatory responses and promote further endothelial injury and pulmonary capillary leakage, resulting in systemic generalization of the inflammation with potentially harmful consequences on the developing preterm brain (10). Hydrogen peroxides are markedly increased in brain tissues of animals exposed to hyperoxia (11). Oxidant stress and systemic inflammation each have independent and synergistic deleterious apoptotic effects on brain microglial cells and immature oligodendrocyte (12)(13)(14). Notably, prolonged supplemental oxygen exposure and systemic inflammation as measured by plasma levels of IL-6 and IL-8 have both been strongly associated with adverse long-term pulmonary and neurodevelopmental outcomes in preterm infants (15)(16)(17)(18)(19).Quality of nutrition early in life has documented beneficial effects on health outcomes later in life (20). Premature...
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