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Charles A Fuller

Publications and source records attributed to Charles A Fuller.

9 recordsLinked to original sources
PubMed2006

Genetic evidence for a neurovestibular influence on the mammalian circadian pacemaker.

The mammalian circadian timing system (CTS) exerts endogenous temporal control over virtually every biochemical, physiological, and neurobiological process. Recent studies have suggested an interrelationship between the neurovestibular system, specifically the macular otoconial gravity receptors, and the CTS. To test for a functional relationship between these 2 seemingly disparate neuronal systems, the authors performed a study to evaluate the influence of the vestibular system on 3 fundamental properties of the CTS: entrainment, photic modulation, and period. The present study used a nonrecombinant mutant mouse, the head-tilt mouse (abbr. het), which lacks otoconia and hence gravity reception, to evaluate CTS function in mice lacking vestibular inputs. Circadian rhythms of body temperature (Tb) and locomotor activity (ACT) were recorded continuously by biotelemetry in het mice as well as wild-type (PWT) controls during exposure to 4 photic regimens: 12:12 LD, DD (0 micromoles s(-1) m(-2)), constant bright light (LL(B); 0.5 micromoles s(-1) m(-2)), and constant dim light (LL(D); 0.02 micromoles s(-1) m(-2)). In DD, the circadian period of the Tb and ACT rhythms was significantly longer (p < 0.001) in het than in PWT mice. In addition, the circadian period of Tb and ACT was significantly longer (p < 0.01) in LL(B) than in DD for both the het and PWT groups, although increasing ambient illuminance (i.e., DD to LL(B)) had a significantly greater (p < 0.01) period-lengthening effect in the PWT group than in the het group. The results of the present study demonstrate for the first time that the vestibular macular gravity receptors influence 2 fundamental properties of the mammalian CTS: (1) the intrinsic circadian pacemaker period and (2) the period-altering response to changes in tonic light intensity. The results of the present study thus provide the first neurobehavioral evidence for a vestibular-circadian interrelationship as well as suggest a novel mechanism underlying the signaling of activity-based nonphotic stimuli to the CTS.

Animals↗
PubMed2005

Parallel and divergent adaptations of rat soleus and plantaris to chronic exercise and hypergravity.

It has been demonstrated that endurance exercise and chronic acceleration, i.e., hypergravity, produce comparable adaptations in a variety of physiological systems, including decreased adiposity, increased energy metabolism, and altered intermediary metabolism. Similar adaptations have not been demonstrated for skeletal muscle per se. To further differentiate between these general responses with respect to gravity and exercise, this study tested the hypothesis that chronic exercise (voluntary wheel running) and chronic acceleration (2 G via centrifugation) will induce similar changes in muscle myosin heavy chain (MHC) isoform expression in rat plantaris, a fast extensor, and in rat soleus, a slow "antigravity" extensor. The experimental design involved four groups of mature male rats (n = 8/group): 1 G and 2 G with running wheels, and 1 G and 2 G controls without running wheels. The primary observations from the study were as follows: 1) 8 wk of 2 G are an adequate stimulus for MHC compositional changes in rat plantaris and soleus muscle; 2) both exercise and +G caused an increase in the slow MHC1 isoform in soleus muscle, suggesting that loading is a primary stimulus for this shift; and 3) 2 G and exercise appeared to have differential effects on the plantaris muscle MHC isoforms, with 2 G causing an increase in MHC2b, and exercise causing a decrease in MHC2b with a concomitant increase in MHC1, suggesting that factors other than enhanced loading, possibly locomotor activity levels, are the primary stimulus for this shift.

Adaptation, Physiological↗
PubMed2005

Insulin-independent pathways mediating glucose uptake in hindlimb-suspended skeletal muscle.

Insulin resistance accompanies atrophy in slow-twitch skeletal muscles such as the soleus. Using a rat hindlimb suspension model of atrophy, we have previously shown that an upregulation of JNK occurs in atrophic muscles and correlates with the degradation of insulin receptor substrate-1 (IRS-1) (Hilder TL, Tou JC, Grindeland RF, Wade CE, and Graves LM. FEBS Lett 553: 63-67, 2003), suggesting that insulin-dependent glucose uptake may be impaired. However, during atrophy, these muscles preferentially use carbohydrates as a fuel source. To investigate this apparent dichotomy, we examined insulin-independent pathways involved in glucose uptake following a 2- to 13-wk hindlimb suspension regimen. JNK activity was elevated throughout the time course, and IRS-1 was degraded as early as 2 wk. AMP-activated protein kinase (AMPK) activity was significantly higher in atrophic soleus muscle, as were the activities of the ERK1/2 and p38 MAPKs. As a comparison, we examined the kinase activity in solei of rats exposed to hypergravity conditions (2 G). IRS-1 phosphorylation, protein, and AMPK activity were not affected by 2 G, demonstrating that these changes were only observed in soleus muscle from hindlimb-suspended animals. To further examine the effect of AMPK activation on glucose uptake, C2C12 myotubes were treated with the AMPK activator metformin and then challenged with the JNK activator anisomycin. While anisomycin reduced insulin-stimulated glucose uptake to control levels, metformin significantly increased glucose uptake in the presence of anisomycin and was independent of insulin. Taken together, these results suggest that AMPK may be an important mediator of insulin-independent glucose uptake in soleus during skeletal muscle atrophy.

AMP-Activated Protein Kinases↗
PubMed2004

Neural plasticity is impaired in cold-exposed hippocampal slices from senescent but not from age-matched presenescent F344 rats.

Near the end of their natural life, many mammals enter a terminal state identifiable by a rapid loss of body weight resulting from hypophagia. This study extends characterization of this senescent state by comparing viability of metabolic mechanisms supporting neural plasticity in hippocampal slices from 24 to 30 month old senescent and age-matched presenescent (body-weight stable) F344 male rats. Half of the slices from each rat were incubated at 22-23 degrees C, and half were immersed in cool incubation medium (12-15 degrees C) immediately after slicing and allowed to passively warm to room temperature over approximately 50 min to impose a cold stressor on recovery mechanisms. Following incubation, CA1 pyramidal cell population spike (PS) amplitudes were measured before and after tetanus. In slices incubated at 22-23 degrees C, the 221.0+/-24.2 % increase in PS amplitude following tetanus in seven slices from five senescent rats was not significantly different from the 202.5+/-23.8% increase in six slices from five age-matched presenescent rats. In contrast, in cold-exposed slices, the 133.8+/-13.1% increase in PS amplitude following tetanus in 14 slices from 10 senescent rats was significantly smaller (p<0.05) than the 184.7+/-10.2% increase in 13 slices from seven age-matched presenescent rats. This smaller PS enhancement in senescent rats cannot be attributed to weight loss because robust potentiation was induced in cold-exposed slices from five food-restricted presenescent rats having a weight loss comparable to their senescent counterparts. Thus, the blunted enhancement observed in cold-exposed slices appears to be a characteristic of senescence.

Aging↗
PubMed2002

Evidence for vestibular regulation of autonomic functions in a mouse genetic model.

Physiological responses to changes in the gravitational field and body position, as well as symptoms of patients with anxiety-related disorders, have indicated an interrelationship between vestibular function and stress responses. However, the relative significance of cochlear and vestibular information in autonomic regulation remains unresolved because of the difficulties in distinguishing the relative contributions of other proprioceptive and interoceptive inputs, including vagal and somatic information. To investigate the role of cochlear and vestibular function in central and physiological responses, we have examined the effects of increased gravity in wild-type mice and mice lacking the POU homeodomain transcription factor Brn-3.1 (Brn-3bPou4f3). The only known phenotype of the Brn-3.1(-/-) mouse is related to hearing and balance functions, owing to the failure of cochlear and vestibular hair cells to differentiate properly. Here, we show that normal physiological responses to increased gravity (2G exposure), such as a dramatic drop in body temperature and concomitant circadian adjustment, were completely absent in Brn-3.1(-/-) mice. In line with the lack of autonomic responses, the massive increase in neuronal activity after 2G exposure normally detected in wild-type mice was virtually abolished in Brn-3.1(-/-) mice. Our results suggest that cochlear and vestibular hair cells are the primary regulators of autonomic responses to altered gravity and provide genetic evidence that these cells are sufficient to alter neural activity in regions involved in autonomic and neuroendocrine control.

Animals↗
PubMed2002

Neurovestibular modulation of circadian and homeostatic regulation: vestibulohypothalamic connection?

Chronic exposure to increased force environments (+G) has pronounced effects on the circadian and homeostatic regulation of body temperature (T(b)), ambulatory activity (Act), heart rate, feeding, and adiposity. By using the Brn 3.1 knockout mouse, which lacks vestibular hair cells, we recently described a major role of the vestibular system in mediating some of these adaptive responses. The present study used the C57BL6JEi-het mouse strain (het), which lacks macular otoconia, to elucidate the contribution of specific vestibular receptors. In this study, eight het and eight WT mice were exposed to 2G for 8 weeks by means of chronic centrifugation. In addition, eight het and eight WT mice were maintained as 1G controls in similar conditions. Upon 2G exposure, the WT exhibited a decrease in T(b) and an attenuated T(b) circadian rhythm. Act means and rhythms also were attenuated. Body mass and food intake were significantly lower than the 1G controls. After 8 weeks, percent body fat was significantly lower in the WT mice (P < 0.0001). In contrast, the het mice did not exhibit a decrease in mean T(b) and only a slight decrease in T(b) circadian amplitude. het Act levels were attenuated similarly to the WT mice. Body mass and food intake were only slightly attenuated in the het mice, and percent body fat, after 8 weeks, was not different in the 2G het group. These results link the vestibular macular receptors with specific alterations in homeostatic and circadian regulation.

Acceleration↗
PubMed2002

Unilateral optic nerve transection alters light response of suprachiasmatic nucleus and intergeniculate leaflet.

The suprachiasmatic nucleus (SCN), the circadian pacemaker, receives photic input directly from the retina to synchronize the pacemaker to the environment. Additionally, the intergeniculate leaflet (IGL), which innervates the SCN, is known to modulate the retinal photic input to the SCN. To further understand the role of the IGL in mediating the photic input to the SCN, this study examined the effects of unilateral optic nerve transection (UONx) on the photic response of the SCN and IGL in adult and neonatal hamsters. UONx led to an overall reduction in light-induced c-Fos expression in the SCN and IGL. The c-Fos expression was greater in the SCN ipsilateral to the remaining eye, despite a symmetrically bilateral retinohypothalamic tract projection as revealed by intraocular injection of horseradish peroxidase. In contrast, UONx led to a greater c-Fos expression in the contralateral IGL. The contralateral IGL of UONx animals also revealed more neuropeptide Y-immunoreactive neurons, while the ipsilateral SCN of these animals exhibited a denser neuropeptide Y terminal field. The neonates with UONx showed a similar pattern with a slight compensation of the photic-induced c-Fos in the SCN. This study suggests that the IGL may have an ipsilateral inhibitory effect in mediating retinal photic input to the SCN.

Animals↗
PubMed2002

Fiber size, type, and myosin heavy chain content in rhesus hindlimb muscles after 2 weeks at 2 G.

BACKGROUND: Fiber atrophy and an increase in the percentage of fast fibers have been observed in Rhesus leg muscles after spaceflight. HYPOTHESIS: Hypergravity will result in muscle fiber hypertrophy and an increase in the percentage of slow fibers. METHODS: Open muscle biopsies were obtained from Rhesus soleus, medial gastrocnemius (MG), and tibialis anterior (TA) muscles before and after 14 d of centrifugation (2 G) and in time-matched controls. Cage activity levels were measured by telemetry. RESULTS: Based on monoclonal antibody binding for myosin heavy chains (MHC), the fastest region of soleus contained a higher proportion of type I+II (27 vs. 13%) and had a tendency for a lower proportion of type I (38 vs. 61%, p = 0.10) fibers after than before centrifugation. There was a higher proportion of type I+II fibers in post- vs. pre-2 G (10 vs. 0.6%) MG biopsies. Fiber type distribution and MHC composition were unaffected in the TA. Overall, mean fiber sizes were unaffected by centrifugation. Average cage activity levels were 36% lower during than before 2 G. CONCLUSIONS: Our hypothesis was rejected. The changes in the proportion of fibers expressing type I MHC are the reverse of that expected with chronic loading of extensors and, paradoxically, are similar to changes observed with chronic unloading, such as occurs during spaceflight, in this primate model. The data are consistent with the observed decrease in total daily activity levels.

Adaptation, Physiological↗