Effects of leptin deficiency on postnatal lung development in mice.

Leptin modulates energy metabolism and lung development. We hypothesize that the effects of leptin on postnatal lung development are volume dependent from 2 to 10 wk of age and are independent of hypometabolism associated with leptin deficiency. To test the hypotheses, effects of leptin deficiency on lung maturation were characterized in age groups of C57BL/6J mice with varying Lep(ob) genotypes. Quasi-static pressure-volume curves and respiratory impedance measurements were performed to profile differences in respiratory system mechanics. Morphometric analysis was conducted to estimate alveolar size and number. Oxygen consumption was measured to assess metabolic rate. Lung volume at 40-cmH(2)O airway pressure (V(40)) increased with age in each genotypic group, and V(40) was significantly (P < 0.05) lower in leptin-deficient (ob/ob) mice beginning at 2 wk. Differences were amplified through 7 wk of age relative to wild-type (+/+) mice. Morphometric analysis showed that alveolar surface area was lower in ob/ob compared with +/+ and heterozygote (ob/+) mice beginning at 2 wk. Unlike the other genotypic groups, alveolar size did not increase with age in ob/ob mice. In another experiment, ob/ob at 4 wk received leptin replacement (5 microg.g(-1) x day(-1)) for 8 days, and expression levels of the Col1a1, Col3a1, Col6a3, Mmp2, Tieg1, and Stat1 genes were significantly increased concomitantly with elevated V(40). Leptin-induced increases in V(40) corresponded with enlarged alveolar size and surface area. Gene expression suggested a remodeling event of lung parenchyma after exogenous leptin replacement. These data support the hypothesis that leptin is critical to postnatal lung remodeling, particularly related to increased V(40) and enlarged alveolar surface area.

Rapid contact call-driven induction of NR2A and NR2B NMDA subunit mRNAs in the auditory thalamus of the budgerigar (Melopsittacus undulatus).

In situ hybridization histochemistry was used to assess the effect of auditory stimulation with natural contact calls on expression of NR2A and NR2B NMDA subunit mRNAs in neurons of the thalamic auditory relay nucleus ovoidalis (Ov) of a vocal learning parrot species, the budgerigar (Melopsittacus undulatus). The results showed that both the core (Ov) and ventromedial shell subdivisions (Ovm) of ovoidalis contained neurons expressing NR2A and NR2B mRNA in no-stimulation control subjects and that the distributions of neurons expressing these subunit mRNAs were very similar in both the core and shell of Ov. Contact call stimulation (5, 30 and 180 min) resulted in substantial increases of 50-60% in the number of neurons expressing NR2A and NR2B mRNAs in both the core and shell. Staining intensity, as measured by the optical density of stained somata approximately doubled compared to controls for both NR2 subunits in the 5 and 30 min conditions, but declined from 30 to 180 min. In all conditions, the density, but not staining intensity, of neurons expressing NR2B exceeded NR2A expression. Furthermore, the density of neurons expressing both subunit mRNAs in call stimulation conditions was greater in the core than in the shell despite the fact that total neuronal density was approximately 20% higher in the shell. Previous experiments have shown that call stimulation is more effective at inducing expression of the immediate early gene zenk in the Ov shell than core; however the present results do not indicate that either NR2A or NR2B mRNA expression mediates this effect since neither subunit exhibits greater expression in Ovm. Ca(++) release is needed for immediate early gene expression, however and, notably, Ovm contains large numbers of neurons containing CGRP, a peptide which has been shown to increase cytosolic Ca(++) levels.