Chronic Sleep Restriction Outcome on the Volumetric Correlates, Neuronal and Glial Number of the Hypoglossal Nucleus in a Rat Model (Preprint)

BACKGROUND Chronic sleep restriction (CSR) is known to result in various changes in brain structures including the dorsal respiratory nuclei of the brain stem. Obstructive sleep apnea has partly been resulted from reduced tone of the muscles including the tongue which are involved in maintaining airway patency during sleep. OBJECTIVE This study aimed at investigating whether CSR may result in structural changes in the hypoglossal nerve nuclei. METHODS Three groups of male rats (each comprising 6) were randomly assigned to CSR, cage control and grid-floor control groups. CSR was imposed using the modified multi-platform box containing water for 18 hours/day for 21 days. At the end of 21 days, the rats’ brain was removed and stained through the modified Giemsa method. The hypoglossal nucleus (HGN) was evaluated through stereological approach. RESULTS The volume of HGN as well as the total number of neuronal and glial cells did not show significant differences between the cage control and the other groups (p=0.3). CONCLUSIONS The current study provided evidence to support that CSR induced by the modified multiple platform approach for 18 hours/day over 21 days in rats, neither results in volume reduction, nor neuronal and glial cells loss in the hypoglossal nuclei in the brain stem.

Effects of Hindlimb Suspension with Stretched or Shortened Muscle Length on Contractile Properties of Rat Soleus

The effects of chronic stretching or shortening of the soleus muscle of adult rats during hindlimb suspension on muscle mass and contractile properties were studied. Rats suspended with the ankle joint immobilized in either a dorsiflexed (Susp-DF. soleus stretched), a plantarflexed position (Susp-PF, soleus shortened), or without immobilization (Susp-Free. soleus shortened) were compared with cage control rats. Suspension-related muscle atrophy was prevented in Susp-DF. The relative muscle weight in Susp-PF was also less than in cage control and Susp-DF. Both isometric maximum twitch tension (Pt) and maximum tetanic tension (Po) in the Susp-Free and Susp-PF were less than control. Both Pt and Po in Susp-DF were normal. The twitch time-to-peak tension and one-half relaxation time tended to be reduced by chronic shortening of the muscle. The rate of tension development during a twitch (dp/dt), expressed as g/s, of Susp-Free group was decreased, but that expressed as g/s/g Pt was greater than controls. That in Susp-DF was subnormal. The fatigue resistance in Susp-Free was normal but was reduced in Susp-DF and Susp-PF. These data suggest that the decreases in the rat soleus mass and maximum tension production and the shift toward a fast-twitch type following hindlimb suspension are prevented by chronic stretching of muscle, although detrimental effect was induced for the fatigue resistance.

Exercise suppresses macrophage antigen presentation

This study determined the effects of exercise on the ability of macrophages (Mφ) to present antigen to T cells. Pathogen-free male Balb/c mice (8 ± 2 wk of age) were randomly assigned to either home cage control, moderate exercise (Mod; 18 m/min, 5% grade, 0.5 h/day), exhaustive exercise (Exh, 18–30 m/min, 3 h/day), or treadmill control groups. The mice underwent treatments for 4 days during peritoneal thioglycolate inflammation. Peritoneal Mφ were harvested, purified, and incubated with chicken ovalbumin (C-OVA; 0–10 mg/ml) for 18 h. Mφ were then cocultured with C-OVA-specific T cells for 48 h, and the supernatants were analyzed via ELISA for interleukin-2 as an indication of Mφ antigen presentation (AP). Exh exhibited suppressed (∼25–34%) Mφ AP across a wide range of C-OVA doses when measured immediately, 3, and 24 h postexercise. In contrast, Mod had reduced Mφ AP only at 3 h postexercise. Mφ AP was also lower in the treadmill control (4–27%) compared with the home cage control group, but was significantly higher than Exh. The reduction in Mφ AP was not due to exercise-induced differences in Mφ number, percentage, or expression of intercellular adhesion molecule-1, B7–2, or major histocompatability complex II, molecules important in AP. In conclusion, our data lend evidence that may help explain the increased incidence of infection observed after prolonged exhaustive exercise or overtraining.

Influence of simulated microgravity on cardiac output and blood flow distribution during exercise

Rats exposed to simulated conditions of microgravity by head-down suspension (HDS) exhibit reductions in aerobic capacity. This may be due to an impaired ability to augment cardiac output and to redistribute blood flow during exercise. The purpose of this investigation was to measure cardiac output and blood flow distribution in rats that were exposed to 14 days of HDS or cage control conditions. Measurements were obtained at rest and during light-intensity (15 m/min) and heavy-intensity (25 m/min; 10% grade) treadmill exercise. Cardiac output was similar in HDS and cage control rats at rest and light exercise but was significantly lower in HDS rats (-33%) during heavy exercise. Soleus muscle blood flow (ml/min) was lower at rest and during exercise in HDS rats; however, when expressed relative to muscle mass (ml.min-1.100 g-1), soleus blood flow was lower only during light exercise. Plantaris muscle blood flow was lower in HDS rats during heavy exercise. Blood flow to the ankle flexor, knee extensor, and knee flexor muscles was not altered by HDS. Blood flow to the spleen and kidney was significantly higher in HDS rats. It was concluded that the reduction in aerobic capacity associated with HDS is due in part to an impaired ability to augment cardiac output during exercise.

Muscle glucose uptake in the rat after suspension with single hindlimb weight bearing

This study was designed to examine the effect of non-weight-bearing conditions and the systemic influences of simulated microgravity on rat hindlimb muscles. For this purpose, rats were suspended (SUS) in a head-down position (45 degrees) with the left hindlimb non-weight bearing (NWB) and the right hindlimb bearing 20% of presuspension body mass (WB). Weight bearing by the SUS-WB limb was accomplished by using a platform connected to a rod in sleeve, cable, and pulley apparatus to which weight could be added. Rats (250–325 g) were assigned to SUS or cage control (CC) conditions for 14 days. The angle between the foot and leg for SUS-WB and CC remained similar (20–30 degrees) throughout the experiment while the SUS-NWB hindlimbs extended to approximately 140 degrees by day 12. On day 14, the soleus, plantaris, and gastrocnemius muscles from the SUS-NWB limbs exhibited significantly lower (P < or = 0.05) masses than presuspension mass values (29, 11, and 21%, respectively). Weight bearing by the SUS-WB limbs prevented the loss of mass by these muscles. In separate groups of SUS and CC rats, 2-deoxyglucose uptake during hindlimb perfusion was significantly higher in both SUS-NWB and SUS-WB hindlimbs at 24,000 microU/ml of insulin compared with CC for all the muscles examined (21–80%). In addition, extracellular space (ml/g) was significantly greater in the soleus muscles from both the SUS-NWB and SUS-WB hindlimbs (64%) compared with CC muscles.

Fatigability and blood flow in the rat gastrocnemius-plantaris-soleus after hindlimb suspension

The purpose of this study was to test the hypothesis that hindlimb suspension increases the fatigability of the soleus during intense contractile activity and determine whether the increased fatigue is associated with a reduced muscle blood flow. Cage-control (C) and 15-day hindlimb-suspended (HS) rats were anesthetized, and either the gastrocnemius-plantaris-soleus (G-P-S) muscle group or the soleus was stimulated (100 Hz, 100-ms trains at 120/min) for 10 min in situ. In the G-P-S preparation, blood flow was measured with radiolabeled microspheres before and at 2 and 10 min of contractile activity. The G-P-S fatigued markedly at this stimulation frequency, and the differences between C and HS animals were not significant until the 9th min of contractile activity. In contrast, the stimulation resulted in faster rates and significantly larger amounts of fatigue in the soleus from HS than from C animals. The atrophied soleus showed significant differences by 1 min of stimulation (C = 70 +/- 1% vs. HS = 57 +/- 2% of peak train force) and remained different at 10 min (C = 64 +/- 4% vs. HS = 45 +/- 2% peak train force). Relative blood flow to the soleus was similar between groups before and during contractile activity (rest: C = 20 +/- 3 vs. HS = 12 +/- 3; 2 min: C = 128 +/- 6 vs. HS = 118 +/- 4; 10 min: C = 123 +/- 11 vs. HS = 105 +/- 11 ml.min-1.100 g-1). In conclusion, these results established that 15 days of HS increased the fatigability of the soleus, but the effect was not caused by a reduced muscle blood flow.

Schedule-Induced Polydipsia and Neocortical Lesions in the Rat

The effects of frontal, midcortical, or occipital lesions on water intake following 23-hr. water deprivation or under conditions of schedule-induced polydipsia within an operant response paradigm were noted. Water intake in the home cage (control) and bar-pressing rates for food were not reliably affected by any of the lesions. Midcortical lesions placed prior to experimentation did not affect the polydipsia, but frontal or occipital lesions placed at the same time attenuated the development of polydipsia. Frontal or occipital lesions placed following the acquisition of polydipsia did not affect the course of polydipsia.