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90 records · Page 5

8-OH-DPAT suppresses vomiting in the cat elicited by motion, cisplatin or xylazine

Vomiting was suppressed in cats pretreated with 8-OH-DPAT and then challenged with an emetic stimulus; motion, xylazine or cisplatin. The antiemetic effect is likely due to stimulation of postsynaptic serotonin-1A receptors. The most parsimonious explanation is that it acts at a convergent structure, presumably at or near the vomiting center. If so, 8-OH-DPAT may block emesis elicited by virtually any other stimulus. A supplementary experiment revealed that lorazepam suppressed motion sickness at a dose that produced ataxia, but did not suppress xylazine-induced emesis. These results do not support the possibility that the antiemetic effects of 8-OH-DPAT were the result of anxiolytic activity.

Lucot, James B.↗

Pineal physiology in microgravity - Relation to rat gonadal function aboard Cosmos 1887

Results are reported from an analysis of pineal glands obtained for five male rats flown aboard an orbiting satellite for their melatonin, serotonin (5-HT), 5-hydroxyindole acetic acid (5-HIA), and calcium content. Plasma 5-HT and 5-HIAA were measured. These parameters were compared to indicators of gonadal function: plasma testosterone concentration and spermatogonia development. Plasma melotonin was found to be low at the time of euthanasia and was not different among the experimental groups. Pineal calcium of flight animals was not different from ground controls. Pineal 5-HT and 5-HIAA in the flight group were significantly higher than those in ground controls. These findings suggest a possible increase in pineal 5-HT turnover in flight animals which may result in increased melatonin secretion. It is argued that the alteration of pinal 5-HT turnover and its expected effects on melatonin secretion may partially explain the lower plasma testosterone levels and 4-11 percent fewer spermatogonia cells observed in flight animals.

Holley, Daniel C.↗

Pharmacological and neurophysiological aspects of space/motion sickness

A motorized motion testing device modeled after a Ferris wheel was constructed to perform motion sickness tests on cats. Details of the testing are presented, and some of the topics covered include the following: xylazine-induced emesis; analysis of the constituents of the cerebrospinal fluid (CSF) during motion sickness; evaluation of serotonin-1A (5-HT sub 1A) agonists; other 5HT receptors; antimuscarinic mechanisms; and antihistaminergic mechanisms. The ability of the following drugs to reduce motion sickness in the cats was examined: amphetamines, adenosinergic drugs, opioid antagonists, peptides, cannabinoids, cognitive enhancers (nootropics), dextromethorphan/sigma ligands, scopolamine, and diphenhydramine.

Lucot, James B.↗

Foods and food constituents that affect the brain and human behavior

Until recently, it was generally believed that brain function was usually independent of day-to-day metabolic changes associated with consumption of food. Although it was acknowledged that peripheral metabolic changes associated with hunger or satiety might affect brain function, other effects of foods on the brain were considered unlikely. However, in 1971, Fernstrom and Wurtman discovered that under certain conditions, the protein-to-carbohydrate ratio of a meal could affect the concentration of a particular brain neurotransmitter. That neurotransmitter, serotonin, participates in the regulation of a variety of central nervous system (CNS) functions including sleep, pain sensitivity, aggression, and patterns of nutrient selection. The activity of other neurotransmitter systems has also been shown to be, under certain conditions, affected by dietary constituents which are given either as ordinary foods or in purified form. For example, the CNS turnover of two catecholamine neurotransmitters, dopamine and norepinephrine, can be altered by ingestion of their amino acid precursor, tyrosine, when neurons that release these monoamines are firing frequently. Similarly, lecithin, a dietary source of choline, and choline itself have been shown to increase the synthesis of acetylcholine when cholinergic neurons are very active. It is possible that other neurotransmitters could also be affected by precursor availability or other, as yet undiscovered peripheral factors governed by food consumption. The effects of food on neurotransmitters and behavior are discussed.

Lieberman, Harris R.↗

Calcitonin control of calcium metabolism during weightlessness

The main objective of this proposal is to elucidate calcitonin role in calcium homeostasis during weightlessness. In this investigation our objectives are to study: the effect of weightlessness on thyroid and serum calcitonin, the effect of weightlessness on the circadian variation of calcitonin in serum and the thyroid gland, the role of light as zeitgeber for calcitonin circadian rhythm, the circadian pattern of thyroid sensitivity to release calcitonin in response to calcium load, and the role of serotonin and norepinephrine in the control of calcitonin release. The main objective of this research/proposal is to establish the role of calcitonin in calcium metabolism during weightlessness condition. Understanding the mechanism of these abnormalities will help in developing therapeutic means to counter calcium imbalance in spaceflights.

Soliman, Karam F. A.↗

Strategies for enhancing catecholamine-mediated neurotransmission

Major findings made during this project period included the following observations: changes in tyrosine availability do affect brain dopamine release, as assessed by in vivo microdialysis, but that neuronal feedback mechanisms limit the durations of this effect except when dopaminergic neurotransmission has been deficient; the circulating hormone TRH markedly stimulates brain dopamine release, an effect probably mediated by its diketopiperazine metabolite; the amount of circulating L-dopa which enters the brain is both enhanced by carbohydrate consumption and suppressed by protein intake (both nutritional effects can be damaging, inasmuch as a sudden rush of L-dopa into the brain can facilitate dyskinesias, while the inhibition of brain L-dopa uptake by proteins suppresses its conversion to brain dopamine; an appropriate mixture of dietary proteins and carbohydrates can obviate both effects); serotonin release from superfused hypothalamic slices is a linear function of available tryptophan levels throughout the normal dynamic range; the daily rhythm in plasma melatonin levels is abnormal both in the sudden infant death syndrome and in women with secondary amenorrhea; tyrosine can potentiate the anorectic effects of widely-used sympathomimetic drugs; newly-described COMT inhibitors can enhance brain dopamine release in vivo; and a cell culture system, based on Y-79 (retinoblast) cells, exists in which melatonin reliably suppresses dopamine release.

Wurtman, Richard J.↗

The value of electrical stimulation as an exercise training modality

Voluntary exercise is the traditional way of improving performance of the human body in both the healthy and unhealthy states. Physiological responses to voluntary exercise are well documented. It benefits the functions of bone, joints, connective tissue, and muscle. In recent years, research has shown that neuromuscular electrical stimulation (NMES) simulates voluntary exercise in many ways. Generically, NMES can perform three major functions: suppression of pain, improve healing of soft tissues, and produce muscle contractions. Low frequency NMES may gate or disrupt the sensory input to the central nervous system which results in masking or control of pain. At the same time NMES may contribute to the activation of endorphins, serotonin, vasoactive intestinal polypeptides, and ACTH which control pain and may even cause improved athletic performances. Soft tissue conditions such as wounds and inflammations have responded very favorably to NMES. NMES of various amplitudes can induce muscle contractions ranging from weak to intense levels. NMES seems to have made its greatest gains in rehabilitation where directed muscle contractions may improve joint ranges of motion correct joint contractures that result from shortening muscles; control abnormal movements through facilitating recruitment or excitation into the alpha motoneuron in orthopedically, neurologically, or healthy subjects with intense sensory, kinesthetic, and proprioceptive information; provide a conservative approach to management of spasticity in neurological patients; by stimulation of the antagonist muscle to a spastic muscle stimulation of the agonist muscle, and sensory habituation; serve as an orthotic substitute to conventional bracing used with stroke patients in lieu of dorsiflexor muscles in preventing step page gait and for shoulder muscles to maintain glenohumeral alignment to prevent subluxation; and of course NMES is used in maintaining or improving the performance or torque producing capability of muscle. NMES in exercise training is our major concern.

Currier, Dean P.↗

Chemical Topography of Efferent Projections from the Median Preoptic Nucleus to Pontine Monoaminergic Cell Groups in the Rat

This study examined efferent output from the median preoptic nucleus (MNPO) to pontine noradrenergic and serotonergic cell groups using an anterograde tracing technique (Phaseolus vulgaris leucoagglutinin, PHA-L) combined with glucose oxidase immunocytochemistry to serotonin (5-HT) or to dopamine-beta-hydroxylase (DBH). Injections of PHA-L into the ventral MNPO resulted in moderate axonal labeling within the region of the B7 and B8 serotonergic groups in the dorsal raphe. PHA-L labeled fibers and punctate processes were observed in close apposition to many of the 5-HT immunoreactive neurons in these regions. In contrast, sparse terminal labeling was found within the B5 group in the raphe pontis nucleus, and only trace fiber labeling observed in the B3 and B6 groups. Efferents from the MNPO also provided moderate innervation to the A6 and A7 noradrenergic groups. PHA-L labeled punctate processes were found most frequently in close apposition to DBH-immunoreactive neurons at mid- to caudal levels of the locus coeruleus. Some labeled axons were also present within the A7 and A5 groups. Additionally, a close apposition between labeled MNPO efferents and 5-HT fibers within the lateral parabrachial nucleus was observed. The results indicate the MNPO provides a topographic innervation of monoaminergic groups in the upper brainstem.

Zardetto-Smith, Andrea M.↗

Neural Control Mechanisms and Body Fluid Homeostasis

The goal of the proposed research was to study the nature of afferent signals to the brain that reflect the status of body fluid balance and to investigate the central neural mechanisms that process this information for the activation of response systems which restore body fluid homeostasis. That is, in the face of loss of fluids from intracellular or extracellular fluid compartments, animals seek and ingest water and ionic solutions (particularly Na(+) solutions) to restore the intracellular and extracellular spaces. Over recent years, our laboratory has generated a substantial body of information indicating that: (1) a fall in systemic arterial pressure facilitates the ingestion of rehydrating solutions and (2) that the actions of brain amine systems (e.g., norepinephrine; serotonin) are critical for precise correction of fluid losses. Because both acute and chronic dehydration are associated with physiological stresses, such as exercise and sustained exposure to microgravity, the present research will aid in achieving a better understanding of how vital information is handled by the nervous system for maintenance of the body's fluid matrix which is critical for health and well-being.

Johnson, Alan Kim↗

The Neuroendocrinology of Thirst and Salt Appetite: Visceral Sensory Signals and Mechanisms of Central Integration

This review examines recent advances in the study of the behavioral responses to deficits of body water and body sodium that in humans are accompanied by the sensations of thirst and salt appetite. Thirst and salt appetite are satisfied by ingesting water and salty substances. These behavioral responses to losses of body fluids, together with reflex endocrine and neural responses, are critical for reestablishing homeostasis. Like their endocrine and neural counterparts, these behaviors are under the control of both excitatory and inhibitory influences arising from changes in osmolality, endocrine factors such as angiotensin and aldosterone, and neural signals from low and high pressure baroreceptors. The excitatory and inhibitory influences reaching the brain require the integrative capacity of a neural network which includes the structures of the lamina terminalis, the amygdala, the perifornical area, and the paraventricular nucleus in the forebrain, and the lateral parabrachial nucleus (LPBN), the nucleus tractus solitarius (NTS), and the area postrema in the hindbrain. These regions are discussed in terms of their roles in receiving afferent sensory input and in processing information related to hydromineral balance. Osmoreceptors controlling thirst are located in systemic Viscera and in central structures that lack the blood-brain barrier. Angiotensin and aldosterone act on and through structures of the lamina terminalis and the amygdala to stimulate thirst and sodium appetite under conditions of hypovolemia. The NTS and LPBN receive neural signals from baroreceptors and are responsible for inhibiting the ingestion of fluids under conditions of increased volume and pressure and for stimulating thirst under conditions of bypovolemia and hypotension. The interplay of multiple facilitory influences within the brain may take the form of interactions between descending angiotensinergic systems originating in the forebrain and ascending adrenergic systems emanating from the hindbrain. Oxytocin and serotonin are additional candidate neuro- chemicals with postulated inhibitory central actions and with essential roles in the overall integration of sensory input within the neural network devoted to maintaining hydromineral balance.

Johnson, Alan Kim↗

Lateral Parabrachial Nucleus Serotonergic Mechanisms and Salt Appetite Induced by Sodium Depletion

This study investigated the effects of bilateral injections of a serotonin (5-HT) receptor agonist into the lateral parabrachial nucleus on the intake of NaCl and water induced by 24-h water deprivation or by sodium depletion followed by 24 h of sodium deprivation (injection of the diuretic furosemide plus 24 h of d sodium-deficient diet). Rats had stainless steel cannulas implanted bilaterally into the LPBN. Bilateral LPBN injections of the serotonergic 5-HT(1/2) receptor antagonist methysergide (4 micro-g/200 nl at each site) increased hypertonic NaCl intake when tested 24 h after sodium depletion and after 24 h of water deprivation. Water intake also increased after bilateral injections of methysergide into the LPBN. In contrast, the intake of a palatable solution (0.06 M sucrose) under body fluid-replete conditions was not changed after bilateral LPBN methysergide injections. The results show that serotonergic mechanisms in the LPBN modulate water and sodium intake induced by volume depletion and sodium loss. The finding that sucrose intake was not affected by LPBN serotonergic blockade suggests that the effects of the methysergide treatment on the intakes of water and NaCl are not due to a mechanism producing a nonspecific enhancement of all ingestive behaviors.

Menani, Jose Vanderlei↗

Nutrients affecting brain composition and behavior

This review examines the changes in brain composition and in various brain functions, including behavior, that can follow the ingestion of particular foods or nutrients. It details those that are best understood: the increases in serotonin, catecholamine, or acetylcholine synthesis that can occur subsequent to food-induced increases in brain levels of tryptophan, tyrosine, or choline; it also discusses the various processes that must intervene between the mouth and the synapse, so to speak, in order for a nutrient to affect neurotransmission, and it speculates as to additional brain chemicals that may ultimately be found to be affected by changes in the availability of their nutrient precursors. Because the brain chemicals best known to be nutrient dependent overlap with those thought to underlie the actions of most of the drugs used to treat psychiatric diseases, knowledge of this dependence may help the psychiatrist to understand some of the pathologic processes occurring in his/her patients, particularly those with appetitive symptoms. At the very least, such knowledge should provide the psychiatrist with objective criteria for judging when to take seriously assertions that particular foods or nutrients do indeed affect behavior (e.g., in hyperactive children). If the food can be shown to alter neurotransmitter release, it may be behaviorally-active; however, if it lacks a discernible neurochemical effect, the likelihood that it really alters behavior is small.

NASA Program Space Medicine↗

Calcium in the regulation of gravitropism by light

The red light requirement for positive gravitropism in roots of corn (Zea mays cv "Merit") provides an entry for examining the participation of calcium in gravitropism. Applications of calcium chelators inhibit the light response. Calcium channel blockers (verapamil, lanthanum) can also inhibit the light response, and a calcium ionophore, A23187, can substitute for light. One can substitute for red light by treatments which have elsewhere been shown to trigger Ca2+ influx into the cytosol, e.g. heat or cold shock. Agents which are known to be agonists of the phosphatidylinositol second messenger system (serotonin, 2,4-dichlorophenoxyacetic acid, deoxycholate) can each partially substitute for the red light, and Li+ can inhibit the light effect. These experiments suggest that the induction of positive gravitropism by red light involves a rise in cytoplasmic Ca2+ concentration, and that a contribution to this end may be made by the phosphatidylinositol second messenger system.

NASA Discipline Number 40-10↗

Exercise and neuromodulators: choline and acetylcholine in marathon runners

Certain neurotransmitters (i.e., acetylcholine, catecholamines, and serotonin) are formed from dietary constituents (i.e., choline, tyrosine and tryptophan). Changing the consumption of these precursors alters release of their respective neurotransmitter products. The neurotransmitter acetylcholine is released from the neuromuscular junction and from brain. It is formed from choline, a common constituent in fish, liver, and eggs. Choline is also incorporated into cell membranes; membranes may likewise serve as an alternative choline source for acetylcholine synthesis. In trained athletes, running a 26 km marathon reduced plasma choline by approximately 40%, from 14.1 to 8.4 uM. Changes of similar magnitude have been shown to reduce acetylcholine release from the neuromuscular junction in vivo. Thus, the reductions in plasma choline associated with strenuous exercise may reduce acetylcholine release, and could thereby affect endurance or performance.

NASA Discipline Regulatory Physiology↗

Functional evidence for the rapid desensitization of 5-HT(3) receptors on vagal afferents mediating the Bezold-Jarisch reflex

The aim of this study was to determine whether 5-hydroxytryptamine (5-HT)(3) receptors on cardiopulmonary afferents mediating the Bezold-Jarisch reflex (BJR) desensitize upon repeated exposure to selective agonists. BJR-mediated falls in heart rate, diastolic arterial blood pressure and cardiac output elicited by the 5-HT(3)-receptor agonists, phenylbiguanide (100 microg/kg, i.v.) or 2-methyl-5-HT (100 microg/kg, i.v.), progressively diminished upon repeated injection in conscious rats. The BJR responses elicited by 5-HT (40 microg/kg, i.v.) were markedly reduced in rats which had received the above injections of phenylbiguanide or 2-methyl-5-HT whereas the BJR responses elicited by L-S-nitrosocysteine (10 micromol/kg, i.v.) were similar before and after the injections of the 5-HT(3) receptor agonists. These findings suggest that tachyphylaxis to 5-HT(3) receptor agonists may be due to the desensitization of 5-HT(3) receptors on cardiopulmonary afferents rather than the impairment of the central or peripheral processing of the BJR.

Non-NASA Center↗

PlantCV v4: Image analysis software for high‐throughput plant phenotyping

PlantCV is an open-source Python project aimed at developing tools to address a range of image-based, plant phenotyping questions. PlantCV has been used for more than 10 years to automate trait collection from image data, and the newest release, PlantCV version 4, continues to lower the barrier to entry for users without substantial coding experience through extensive example use-case tutorials and simplified installation. In addition to usability, we document added functionality since the release of PlantCV v2, including support for more image types such as fluorescence, thermal, and hyperspectral data. Finally, we describe the development of a new subpackage focused on morphological trait measurements like leaf angle, and demonstrate its utility as compared to more manual methods of data collection.

Schuhl, Haley [Donald Danforth Plant Science Cente↗

Blockade of 5-hydroxytryptamine3 receptors prevents cisplatin-induced but not motion- or xylazine-induced emesis in the cat

5-Hydroxytryptamine3 antagonists have been reported to prevent emesis elicited by cisplatin and radiation. This study investigated the possibility that drugs with this mechanism of action may be useful in preventing emesis elicited by other stimuli. The drugs ICS 205-930 (0.1 and 1.0 mg/kg) and MDL 72222 (0.1 and 1.0 mg/kg) were administered SC to cats before challenging them with either provocative motion or an emetic dose of xylazine. In no instance was a significant reduction in emesis evident. Zacopride was also administered before motion testing (0.01 to 10.0 mg/kg) and found to not have efficacy. To test the possibility that species or route of administration were factors in the negative results, 1.0 mg/kg of ICS 205-930 was administered SC before IV infusion of 7.5 mg/kg of cisplatin. There was a total suppression of emesis for the duration of the six-hour observation periods. This result verifies other work which found 5-hydroxytryptamine3 antagonists to be effective in preventing emesis elicited by cancer chemotherapeutic treatments. However, there is no evidence that they are effective in other syndromes, such as motion sickness and xylazine-induced emesis.

NASA Discipline Number 16-10↗