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Biomedical subjects

C A Fuller

Publications and source records attributed to C A Fuller.

At least 73 records · Page 4Linked to original sources

The retinohypothalamic projection and oxidative metabolism in the suprachiasmatic nucleus of primates and tree shrews.

This study compared the patterns of retinal projections and oxidative metabolism in the hypothalamus of squirrel monkeys, Bonnet macaques, and tree shrews. Intraocular injections of horseradish peroxidase in primates demonstrated that retinal terminals were present from the anterior to posterior poles of the suprachiasmatic nucleus (SCN). The terminals were primarily located in the ventral and ventrolateral regions of the SCN. In addition, there was a relatively even density and distribution of retinal terminals between the ipsilateral and contralateral projections. The pattern of oxidative metabolism in the hypothalamus of the primates examined demonstrated that the SCN is highly metabolic relative to the surrounding area, and distinct regions of the SCN exhibit clear differences in metabolism. These distinct metabolic regions may reflect functional subdivisions within the SCN. In addition, elevated metabolism is found along the hypothalamo-optic chiasm border. The retinal projection to the hypothalamus in tree shrews was very different from that of the primates examined. The contralateral retinal projection was very dense, but the ipsilateral retinal projection was very sparse. Retinal terminals were primarily distributed along the lateral border of the SCN. Both the SCN and the region lateral to the SCN exhibited elevated oxidative metabolism relative to the surrounding hypothalamus.

Animals↗

Neuronal activity in hypothalamic nuclei of obese and lean Zucker rats.

Central neural activity was assessed by measuring relative cytochrome oxidase (CO) activity in the ventromedial nucleus (VMN; thermogenesis regulation), the parvocellular paraventricular nucleus (PVN; feeding regulation), and the magnocellular PVN (secretion of vasopressin and oxytocin) in 10 age-matched pairs of 39- to 42-day-old Zucker rats. When obese (fa/fa) were compared to lean (Fa/Fa) rats, relative CO activity was significantly lower (approximately 10 percent) in the VMN and parvocellular PVN, but not in the magnocellular PVN. Cell diameters did not differ. To determine if there were corresponding differences in levels or release of hypothalamic monoamines, we compared 7 pairs of 90- to 94-day-old lean (Fa/?) and obese (fa/fa) rats at rest and after 2 h of 9 degrees C. Tissue punches from frozen PVN, VMN, and preoptic area (the latter being a site of thermosensitive units modulating VMN output) were assayed. In obese vs. lean noncold-exposed rats, we observed lower concentrations of: 5-hydroxyindoleacetic acid (5HIAA; metabolite of serotonin, 5HT) in the VMN; 3-methoxy-4-hydroxyphenylglycol (MHPG; metabolite of norepinephrine, NE) and NE + MHPG (index of total NE) in the preoptic area; and 3,4-dihydroxyphenylacetic acid (DOPAC; metabolite of dopamine, DA) in the PVN. Additionally, in the VMN, cold exposure resulted in: elevated concentrations of MHPG and MHPG + NE in both lean and obese rats; elevated concentrations of 5HT, 5HIAA, and 5HT + 5HIAA in obese rats, with no significant changes in these variables in lean animals; decreased ratio of 5HIAA/5HT in obese rats and increased ratio in leans. In the preoptic region, cold exposure led to increased concentrations of MHPG, NE + MHPG, 5HT, and 5HT + 5HIAA in obese but not lean rats. In the PVN, 5HT concentrations were increased in cold-exposed obese but not lean rats. Our data support the hypothesis that neuronal activity in obese rats differs from that of lean rats at rest and during cold exposure and suggest that several monoamine systems play a role in such differences.

Adipose Tissue, Brown↗

The effect of hyperdynamic fields on the oxidative metabolism of the paraventricular nucleus.

An important issue in space biology and medicine is understanding the effect of gravitational changes on the mechanisms that regulate fluid homeostasis. The results of this study show that following 7 d exposure to a 2 G or 3 G hyperdynamic field, rats exhibited a linear increase in the cytochrome oxidase staining of neurons in the paraventricular nucleus (PVN). The elevated oxidative metabolism in the PVN suggests that there was an increase in the manufacturing and release of vasopressin into the plasma in response to a perceived hypovolemic condition caused by increased hydrostatic pressure and redistribution of fluid to the periphery. Since vasopressin also has widespread cardiovascular effects, it will be important to understand the relationship between vasopressin and altered gravitational fields.

Animals↗

The retinohypothalamic tract in the cat: retinal ganglion cell morphology and pattern of projection.

The pattern of retinal projection to the hypothalamus and the morphological properties of the retinal ganglion cells that comprise the retinohypothalamic tract have been examined in the cat. Intraocular injections of horseradish peroxidase revealed a dense retinal projection to the ventral suprachiasmatic nucleus; however, lighter projections were seen in the dorsal suprachiasmatic nucleus, and in hypothalamic regions both dorsal and lateral to the suprachiasmatic nucleus. Intrasuprachiasmatic nucleus injections of horseradish peroxidase retrogradely labelled retinal ganglion cells that were small to medium in soma size. The labelled ganglion cells exhibited long thin dendrites that were sparsely branched. The labelled retinal ganglion cells exhibited a significant change in soma size associated with retinal eccentricity. The morphological characteristics of the ganglion cells that project to the suprachiasmatic nucleus are similar to those of gamma cells.

Animals↗

Effects of microgravity on brain neurotransmitter receptors.

Neurotransmitter receptor binding and Na+, K+-ATPase activity were examined in the brains of six rats exposed to 7 days of microgravity during the flight of Spacelab 3. The same variables were examined in a group of six ground control rats. 5-HT1 receptor number in the hippocampus was significantly elevated by exposure to the microgravity environment, and cortical sodium-potassium pump activity was significantly depressed. A marginal depression in dopamine D-2 binding in the striatum was noted. Dopamine and 5-HT binding in a wide variety of other central regions, in addition to GABAA, muscarinic acetylcholine, adenosine A1, and opiate receptor binding, and adrenoceptor binding, was unaffected by microgravity exposure.

Animals↗

The biological clock of Neurospora in a microgravity environment.

The circadian rhythm of conidiation in Neurospora crassa is thought to be an endogenously derived circadian oscillation; however, several investigators have suggested that circadian rhythms may, instead, be driven by some geophysical time cue(s). An experiment was conducted on space shuttle flight STS-9 in order to test this hypothesis; during the first 7-8 cycles in space, there were several minor alterations observed in the conidiation rhythm, including an increase in the period of the oscillation, an increase in the variability of the growth rate and a diminished rhythm amplitude, which eventually damped out in 25% of the flight tubes. On day seven of flight, the tubes were exposed to light while their growth fronts were marked. Some aspect of the marking process reinstated a robust rhythm in all the tubes which continued throughout the remainder of the flight. These results from the last 86 hours of flight demonstrated that the rhythm can persist in space. Since the aberrant rhythmicity occurred prior to the marking procedure, but not after, it was hypothesized that the damping on STS-9 may have resulted from the hypergravity pulse of launch. To test this hypothesis, we conducted investigations into the effects of altered gravitational forces on conidiation. Exposure to hypergravity (via centrifugation), simulated microgravity (via the use of a clinostat) and altered orientations (via alterations in the vector of a 1 g force) were used to examine the effects of gravity upon the circadian rhythm of conidiation.

Biological Clocks↗

Gravitational biology and the mammalian circadian timing system.

Mammals have evolved under the influence of many selective pressures. Two of these pressures have been the static force of gravity and the daily variations in the environment due to the rotation of the earth. It is now clear that each of these pressures has led to specific adaptations which influence how organisms respond to changes in either gravity or daily time cues. However, several unpredicted responses to altered gravitational environments occur within the homeostatic and circadian control systems. These results may be particularly relevant to biological and medical issues related to spaceflight. This paper demonstrates that the homeostatic regulation of rat body temperature, heart rate, and activity become depressed following exposure to a 2 G hyperdynamic field, and recovers within 5-6 days. In addition, the circadian rhythms of these same variables exhibit a depression of rhythm amplitude; however, recovery required a minimum of 7 days.

Adaptation, Physiological↗

Temperature regulation in rats exposed to a 2 G field.

The regulation of body temperature involves both homeostatic and circadian control systems. Both systems are influenced by exposure to hyperdynamic fields and demonstrate acute responses that eventually recover to an adapted level. This experiment examined both the homeostatic and circadian responses of body temperature to a separate environmental challenge (high frequency light/dark cycles) during exposure to a 2 G hyperdynamic field.

Animals↗

The postnatal development of oxidative metabolism in the suprachiasmatic nucleus of the rat.

This study examined the postnatal development of oxidative metabolism in the rat suprachiasmatic nucleus. The cytochrome oxidase technique was used to reveal the pattern of metabolic development. The cytochrome oxidase reactivity in suprachiasmatic nucleus is above background at birth and coincides with the Nissl-stained borders of the suprachiasmatic nucleus. The suprachiasmatic nucleus gradually increases in cytochrome oxidase intensity through 24 days of age. At 28 days of age the dorsal border in the middle suprachiasmatic nucleus decreases in cytochrome oxidase reactivity. This decrease in cytochrome oxidase reactivity proceeds in a posterior direction until the entire posterior portion of the suprachiasmatic nucleus is devoid of intense cytochrome oxidase reactivity at 42 days of age. Intense cytochrome oxidase was not confined within the Nissl borders of suprachiasmatic nucleus at 28 days of age, but continued laterally beyond the suprachiasmatic nucleus border directly dorsal to the optic chiasm. This lateral region became more intense and extensive through 42 days of age. Therefore, the suprachiasmatic nucleus exhibits a distinct pattern of development in oxidative metabolism. This pattern of metabolic development may be important for understanding the development of overt circadian rhythms.

Animals↗

The response of suprachiasmatic neurons of the rat hypothalamus to photic and nicotinic stimuli.

Single neurons in the suprachiasmatic nucleus (SCN) and surrounding hypothalamic nuclei of the rat were characterized functionally and pharmacologically. Photically responsive neurons of the SCN typically exhibited a similar response to intravenous nicotine. The response to nicotine was antagonized by the nicotinic blocker, mecamylamine. Nicotinic blockade either eliminated or even reversed the sign of the photic response during subsequent photic stimulation. This constellation of results was not seen in neurons of adjacent hypothalamic regions.

Action Potentials↗

Effects of light intensity on the circadian temperature and feeding rhythms in the squirrel monkey.

The circadian rhythms of body temperature and feeding appear to be timed by separate pacemakers. Tonic administration of light has been used to investigate the response of the pacemaker timing behavioral rhythms; however, the response of the body temperature rhythm has not been similarly examined. This study investigates the circadian timing of the body temperature rhythm under conditions of different light intensity. We simultaneously recorded the patterns of both feeding and body temperature in squirrel monkeys free-running in an environment free of external time cues. In each lighting condition, the periods of the body temperature and feeding rhythms were identical. In constant bright light the rhythm periods were longer than when the animals were exposed to constant dim light. In addition, the variability of the periods was dependent on light intensity. The feeding rhythm period variance of animals in constant bright light was smaller than when in dim light. Conversely, the period of the free-running body temperature rhythm exhibited more variability in bright light than in dim light. Further, in each condition, there were changes in phase angle relationship between feeding and body temperature which were qualitatively similar to those observed in humans, although quantitatively smaller in magnitude. Thus, in the squirrel monkey, tonic light studies reveal that the mean circadian period of the body temperature and feeding rhythms are similar. However, changes in phase relationship, and differential rhythm period stabilities suggest differences in the period of the underlying, tightly coupled pacemakers.

Animals↗

Role of heat loss and heat production in generation of the circadian temperature rhythm of the squirrel monkey.

To study heat production and heat loss in determination of the daily body temperature rhythm, we examined colonic temperature, skin (tail, foot and abdomen) temperatures and oxygen consumption in chair-restrained squirrel monkeys maintained in isolation in an environmental chamber with a 24-hr light-dark cycle (LD 12:12), maintained at a constant thermoneutral temperature (26 degrees C). In all experiments repeated high amplitude (2 degrees C) diurnal rhythms in colonic temperature were observed. Heat loss, estimated from changes in skin temperature, also displayed a circadian rhythm, although there was considerable variation in waveform. On average, a rhythm in heat production, indicated by changes in the rate of oxygen consumption, was also present. However, a large degree of variability was seen in oxygen consumption, and in several cycles from various animals there were no observable 24-hr rhythms. The circadian body temperature rhythm is thus not simply a consequence of daily changes in metabolism, but rather a regulated response that involves both heat production and heat loss.

Animals↗