pathology; however, direct comparisons of popular models are not available. In this study, we compared adenine-induced nephropathy and 5/6 nephrectomy models. Curzerene Both models produced equivalent levels of muscle atrophy and mitochondrial impairment, but the adenine model exhibited lower mortality rates, higher consistency in uremic toxin levels, and dysregulated phosphate homeostasis compared with the 5/6 nephrectomy model.We used male BTBR mice carrying the Lepob mutation, which are subject to severe and progressive obesity and diabetes beginning at 6 weeks of age, to examine the influence of one specific manifestation of sleep apnea, intermittent hypoxia, on male urinary voiding physiology and genitourinary anatomy. A custom device was used to deliver continuous normoxia (NX, control) or intermittent hypoxia (IH) to wild type and Lepob/ob (mutant) mice for 2 weeks. Intermittent hypoxia was delivered during the 12-hour inactive (lighted) period in the form of 90 sec of 6% O2 followed by 90 sec of room air. Continuous room air was delivered during the 12-hour active (dark) period. We then evaluated genitourinary anatomy and physiology. As expected for the type 2 diabetes phenotype, mutant mice consume more food and water, weighed more, and voided more frequently and in larger urine volumes. They also have larger bladder volumes but smaller prostates, seminal vesicles, and urethras than wild type mice. IH decreases food consumption and increases bladder relative weight independent of genotype and increases urine glucose concentration in mutant mice. When evaluated based on genotype (NX+IH), the incidence of pathogenic bacteriuria is greater in mutant than wild type mice, and among mice exposed to IH, bacteriuria incidence is greater in mutant than wild type mice. We conclude that IH exposure and type 2 diabetes can act independently and together to modify male mouse urinary function.Humans, primates, and rodents with cervical spinal cord injury (SCI) show permanent sensorimotor dysfunction of the upper/forelimb as consequence of axonal damage and local neuronal death. This work aimed at characterizing a model of cervical SCI in domestic pigs in which hemisection with excision of 1 cm of spinal cord was performed to reproduce the loss of neural tissue observed in human neuropathology. Posture and motor control were assessed over 3 months by scales and kinematics of treadmill locomotion. Histological measurements included lesion length, atrophy of the adjacent spinal cord segments, and neuronal death. In some animals, the retrograde neural tracer aminostilbamidine was injected in segments caudal to the lesion to visualize propriospinal projection neurons. Neuronal loss extended for 4-6 mm from the lesion borders and was more severe in the ipsilateral, caudal spinal cord stump. Axonal Wallerian degeneration was observed caudally and rostrally, associated with marked atrophy of the white matter in the spinal cord segments adjacent to the lesion. The pigs showed chronic monoplegia or severe monoparesis of the foreleg ipsilateral to the lesion, whereas the trunk and the other legs had postural and motor impairments that substantially improved during the first month post-lesion. Adaptations of the walking cycle such as those reported for rats and humans ameliorated the negative impact of focal neurological deficits on locomotor performance. These results provide a baseline of behavior and histology in a porcine model of cervical spinal cord hemisection that can be used for translational research in SCI therapeutics.Because patients with chronic obstructive pulmonary disease (COPD) are often physically inactive, it is still unclear whether the lower respiratory capacity in the locomotor muscles of these patients is due to cigarette smoking per se or is secondary to physical deconditioning. Accordingly, the purpose of this study was to examine mitochondrial alterations in the quadriceps muscle of 10 mice exposed to 8 mo of cigarette smoke, a sedentary mouse model of emphysema, and 9 control mice, using immunoblotting, spectrophotometry, and high-resolution respirometry in permeabilized muscle fibers. Mice exposed to smoke displayed a twofold increase in the oxidative stress marker, 4-HNE, (P less then 0.05) compared with control mice. This was accompanied by significant decrease in protein expression of UCP3 (65%), ANT (58%), and mitochondrial complexes II-V (∼60%-75%). In contrast, maximal ADP-stimulated respiration with complex I and II substrates (CON 23.6 ± 6.6 and SMO 19.2 ± 8.2 ρM·mg-1·s-1) or octanoylcarnitine (Cletal muscle phenotype, cigarette smoke does not directly contribute to mitochondrial dysfunction. With this evidence, we demonstrate the critical role of physical inactivity in cigarette smoke-related skeletal muscle dysfunction.This experiment investigated which hypothalamic nuclei were activated by a dose of leptin that inhibited food intake. Foodnot intake, energy expenditure, respiratory exchange ratio (RER), and intrascapular brown adipose tissue (IBAT) temperature were measured in male and female Sprague Dawley rats for 36 h following an intraperitoneal injection of 0, 50, 200, 500, or 1,000 µg leptin/kg with each rat tested with each dose of leptin in random order. In both males and females, RER and 12-h food intake were inhibited only by 1,000 µg leptin/kg, but there was no effect on energy expenditure or IBAT temperature. At the end of the experiment, phosphorylated signal transducer and activator of transcription 3 (pSTAT3) immunoreactivity was measured 1 h after injection of 0, 50, 500, or 1,000 µg leptin/kg. In male rats, the lowest dose of leptin produced a maximal activation of STAT3 in the Arc and nucleus of the solitary tract (NTS). There was no response in the dorsomedial hypothalamus, but there was a progressive increase in ventromedial nucleus of the hypothalamus (VMH) pSTAT3 with increasing doses of leptin. In female rats, there was no significant change in Arc and pSTAT3 NTS activation was maximal with 500 mg leptin/kg, but only the highest dose of leptin increased VMH pSTAT3. These results suggest that the VMH plays an important role in the energetic response to elevations of circulating leptin but do not exclude the possibility that multiple nuclei provide the appropriate integrated response to hyperleptinemia.NEW & NOTEWORTHY The results of this experiment show that doses of leptin too small to inhibit food intake produce a maximal response to leptin in the arcuate nucleus. By contrast the VMH shows a robust response that correlates with inhibition of food intake. This suggests that the VMH plays an important role in the energetic response to hyperleptinemia.