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At least 847 records · Page 47

Effects of hypergravity exposure on the developing central nervous system: possible involvement of thyroid hormone

The present study examined the effects of hypergravity exposure on the developing brain and specifically explored the possibility that these effects are mediated by altered thyroid status. Thirty-four timed-pregnant Sprague-Dawley rats were exposed to continuous centrifugation at 1.5 G (HG) from gestational Day 11 until one of three key developmental points: postnatal Day (P) 6, P15, or P21 (10 pups/dam: 5 males/5 females). During the 32-day centrifugation, stationary controls (SC, n = 25 dams) were housed in the same room as HG animals. Neonatal body, forebrain, and cerebellum mass and neonatal and maternal thyroid status were assessed at each time point. The body mass of centrifuged neonates was comparatively lower at each time point. The mass of the forebrain and the mass of the cerebellum were maximally reduced in hypergravity-exposed neonates at P6 by 15.9% and 25.6%, respectively. Analysis of neonatal plasma suggested a transient hypothyroid status, as indicated by increased thyroid stimulating hormone (TSH) level (38.6%) at P6, while maternal plasma TSH levels were maximally elevated at P15 (38.9%). Neither neonatal nor maternal plasma TH levels were altered, suggesting a moderate hypothyroid condition. Thus, continuous exposure of the developing rats to hypergravity during the embryonic and neonatal periods has a highly significant effect on the developing forebrain and cerebellum and neonatal thyroid status (P < 0.05, Bonferroni corrected). These data are consistent with the hypothesized role of the thyroid hormone in mediating the effect of hypergravity in the developing central nervous system and begin to define the role of TH in the overall response of the developing organism to altered gravity.

Non-NASA Center↗

Defining the cortical visual systems: "what", "where", and "how"

The visual system historically has been defined as consisting of at least two broad subsystems subserving object and spatial vision. These visual processing streams have been organized both structurally as two distinct pathways in the brain, and functionally for the types of tasks that they mediate. The classic definition by Ungerleider and Mishkin labeled a ventral "what" stream to process object information and a dorsal "where" stream to process spatial information. More recently, Goodale and Milner redefined the two visual systems with a focus on the different ways in which visual information is transformed for different goals. They relabeled the dorsal stream as a "how" system for transforming visual information using an egocentric frame of reference in preparation for direct action. This paper reviews recent research from psychophysics, neurophysiology, neuropsychology and neuroimaging to define the roles of the ventral and dorsal visual processing streams. We discuss a possible solution that allows for both "where" and "how" systems that are functionally and structurally organized within the posterior parietal lobe.

NASA Discipline Space Human Factors↗

Peptides and neurotransmitters that affect renin secretion

Substance P inhibits renin secretion. This polypeptide is a transmitter in primary afferent neurons and is released from the peripheral as well as the central portions of these neurons. It is present in afferent nerves from the kidneys. Neuropeptide Y, which is a cotransmitter with norepinephrine and epinephrine, is found in sympathetic neurons that are closely associated with and presumably innervate the juxtagolmerular cells. Its effect on renin secretion is unknown, but it produces renal vasoconstriction and natriuresis. Vasoactive intestinal polypeptide (VIP) is a cotransmitter with acetylocholine in cholinergic neurons, and this polypeptide stimulates renin secretion. We cannot find any evidence for its occurence in neurons in the kidneys, but various stimuli increase plasma VIP to levels comparable to those produced by doses of exogenous VIP which stimulated renin secretion. Neostigmine increases plasma VIP and plasma renin activity, and the VIP appears to be responsible for the increase in renin secretion, since the increase is not blocked by renal denervation or propranolol. Stimulation of various areas in the brain produces sympathetically mediated increases in plasma renin activity associated with increases in blood pressure. However, there is pharmacological evidence that the renin response can be separated from the blood pressure response. In anaesthetized dogs, drugs that increase central serotonergic discharge increase renin secretion without increasing blood pressure. In rats, activation of sertonergic neurons in the dorsal raphe nucleus increases renin secretion by a pathway that projects from this nucleus to the ventral hypothalamus, and from there to the kidneys via the sympathetic nervous system. The serotonin releasing drug parachloramphetamine also increases plasma VIP, but VIP does not appear to be the primary mediator of the renin response. There is preliminary evidence that the serotonergic neurons in the dorsal raphe nucleus are part of the pathway by which psychosocial stimuli increase renin secretion.

Review↗

Development of Algorithms for Control of Humidity in Plant Growth Chambers

Algorithms were developed to control humidity in plant growth chambers used for research on bioregenerative life support at Kennedy Space Center. The algorithms used the computed water vapor pressure (based on measured air temperature and relative humidity) as the process variable, with time-proportioned outputs to operate the humidifier and de-humidifier. Algorithms were based upon proportional-integral-differential (PID) and Fuzzy Logic schemes and were implemented using I/O Control software (OPTO-22) to define and download the control logic to an autonomous programmable logic controller (PLC, ultimate ethernet brain and assorted input-output modules, OPTO-22), which performed the monitoring and control logic processing, as well the physical control of the devices that effected the targeted environment in the chamber. During limited testing, the PLC's successfully implemented the intended control schemes and attained a control resolution for humidity of less than 1%. The algorithms have potential to be used not only with autonomous PLC's but could also be implemented within network-based supervisory control programs. This report documents unique control features that were implemented within the OPTO-22 framework and makes recommendations regarding future uses of the hardware and software for biological research by NASA.

Costello, Thomas A.↗

Postural control model interpretation of stabilogram diffusion analysis

Collins and De Luca [Collins JJ. De Luca CJ (1993) Exp Brain Res 95: 308-318] introduced a new method known as stabilogram diffusion analysis that provides a quantitative statistical measure of the apparently random variations of center-of-pressure (COP) trajectories recorded during quiet upright stance in humans. This analysis generates a stabilogram diffusion function (SDF) that summarizes the mean square COP displacement as a function of the time interval between COP comparisons. SDFs have a characteristic two-part form that suggests the presence of two different control regimes: a short-term open-loop control behavior and a longer-term closed-loop behavior. This paper demonstrates that a very simple closed-loop control model of upright stance can generate realistic SDFs. The model consists of an inverted pendulum body with torque applied at the ankle joint. This torque includes a random disturbance torque and a control torque. The control torque is a function of the deviation (error signal) between the desired upright body position and the actual body position, and is generated in proportion to the error signal, the derivative of the error signal, and the integral of the error signal [i.e. a proportional, integral and derivative (PID) neural controller]. The control torque is applied with a time delay representing conduction, processing, and muscle activation delays. Variations in the PID parameters and the time delay generate variations in SDFs that mimic real experimental SDFs. This model analysis allows one to interpret experimentally observed changes in SDFs in terms of variations in neural controller and time delay parameters rather than in terms of open-loop versus closed-loop behavior.

NASA Program Biomedical Research and Countermeasur↗

Simian virus 40, poliovirus vaccines, and human cancer: research progress versus media and public interests

From 1955 through early 1963, millions of people were inadvertently exposed to simian virus 40 (SV40) as a contaminant of poliovirus vaccines; the virus had been present in the monkey kidney cultures used to prepare the vaccines and had escaped detection. SV40 was discovered in 1960 and subsequently eliminated from poliovirus vaccines. This article reviews current knowledge about SV40 and considers public responses to reports in the media. SV40 is a potent tumour virus with broad tissue tropism that induces tumours in rodents and transforms cultured cells from many species. It is also an important laboratory model for basic studies of molecular processes in eukaryotic cells and mechanisms of neoplastic transformation. SV40 neutralizing antibodies have been detected in individuals not exposed to contaminated poliovirus vaccines. There have been many reports of detection of SV40 DNA in human tumours, especially mesotheliomas, brain tumours and osteosarcomas; and DNA sequence analyses have ruled out the possibility that the viral DNA in tumours was due to laboratory contamination or that the virus had been misidentified. However, additional studies are necessary to prove that SV40 is the cause of certain human cancers. A recently published review article evaluated the status of the field and received much media attention. The public response emphasized that there is great interest in the possibility of health risks today from vaccinations received in the past.

Review, Tutorial↗

Visual circuits of the avian telencephalon: evolutionary implications

Birds and primates are vertebrates that possess the most advanced, efficient visual systems. Although lineages leading to these two classes were separated about 300 million years ago, there are striking similarities in their underlying neural mechanisms for visual processing. This paper discusses such similarities with special emphasis on the visual circuits in the avian telencephalon. These similarities include: (1) the existence of two parallel visual pathways and their distinct telencephalic targets, (2) anatomical and functional segregation within the visual pathways, (3) laminar organization of the telencephalic targets of the pathways (e.g. striate cortex in primates), and (4) possible interactions between multiple visual areas. Additional extensive analyses are necessary to determine whether these similarities are due to inheritance from a common ancestral stock or the consequences of convergent evolution based on adaptive response to similar selective pressures. Nevertheless, such a comparison is important to identify the general and specific principles of visual processing in amniotes (reptiles, birds, and mammals). Furthermore, these principles in turn will provide a critical foundation for understanding the evolution of the brain in amniotes.

Review, Tutorial↗

Growing crops for space explorers on the moon, Mars, or in space

An option in the long-duration exploration of space, whether on the Moon or Mars or in a spacecraft on its way to Mars or the asteroids, is to utilize a bioregenerative life-support system in addition to the physicochemical systems that will always be necessary. Green plants can use the energy of light to remove carbon dioxide from the atmosphere and add oxygen to it while at the same time synthesizing food for the space travelers. The water that crop plants transpire can be condensed in pure form, contributing to the water purification system. An added bonus is that green plants provide a familiar environment for humans far from their home planet. The down side is that such a bioregenerative life-support system--called a controlled environment life-support system (CELSS) in this paper--must be highly complex and relatively massive to maintain a proper composition of the atmosphere while also providing food. Thus, launch costs will be high. Except for resupply and removal of nonrecycleable substances, such a system is nearly closed with respect to matter but open with respect to energy. Although a CELSS facility is small compared to the Earth's biosphere, it must be large enough to feed humans and provide a suitable atmosphere for them. A functioning CELSS can only be created with the help of today's advanced technology, especially computerized controls. Needed are energy for light, possibly from a nuclear power plant, and equipment to provide a suitable environment for plant growth, including a way to supply plants with the necessary mineral nutrients. All this constitutes the biomass production unit. There must also be food preparation facilities and a means to recycle or dispose of waste materials and there must be control equipment to keep the facility running. Humans are part of the system as well as plants and possibly animals. Human brain power will often be needed to keep the system functional in spite of the best computer-driven controls. The particulars of a CELSS facility depend strongly on where it is to be located. The presence of gravity on the Moon and Mars simplifies the design for a facility on those bodies, but a spacecraft in microgravity is a much more challenging environment. One problem is that plants, which are very sensitive to gravity, might not grow and produce food in the virtual absence of gravity. However, the experience with growing super-dwarf wheat in the Russian space station Mir, while not entirely successful because of the sterile wheat heads, was highly encouraging. The plants grew well for 123 days, producing more biomass than had been produced in space before. This was due to the high photon flux available to the plants and the careful control of substrate moisture. The sterile heads were probably due to the failure to remove the gaseous plant hormone, ethylene, from the Mir atmosphere. Since ethylene can easily be removed, it should be possible to grow wheat and other crops in microgravity with the production of viable seeds. On the ground Biosphere-2 taught us several lessons about the design and construction of a CELSS facility, but Bios-3 came much closer to achieving the goals of such a facility. Although stability was never completely reached, Bios-3 was much more stable than Biosphere-2 apparently because every effort was made to keep the system simple and to use the best technology available to maintain control. Wastes were not recycled in Bios-3 except for urine, and inedible plant materials were incinerated to restore CO2 to the atmosphere. Since much meat (about 20% of calories) was imported, closure in the Bios-3 experiments was well below 100%. But then, a practical CELSS on the Moon might also depend on regular resupply from Earth. Several important lessons have been learned from the CELSS research described in this review.

Review↗

EEG and ocular correlates of circadian melatonin phase and human performance decrements during sleep loss

The aim of this study was to quantify the associations between slow eye movements (SEMs), eye blink rate, waking electroencephalogram (EEG) power density, neurobehavioral performance, and the circadian rhythm of plasma melatonin in a cohort of 10 healthy men during up to 32 h of sustained wakefulness. The time course of neurobehavioral performance was characterized by fairly stable levels throughout the first 16 h of wakefulness followed by deterioration during the phase of melatonin secretion. This deterioration was closely associated with an increase in SEMs. Frontal low-frequency EEG activity (1-7 Hz) exhibited a prominent increase with time awake and little circadian modulation. EEG alpha activity exhibited circadian modulation. The dynamics of SEMs and EEG activity were phase locked to changes in neurobehavioral performance and lagged the plasma melatonin rhythm. The data indicate that frontal areas of the brain are more susceptible to sleep loss than occipital areas. Frontal EEG activity and ocular parameters may be used to monitor and predict changes in neurobehavioral performance associated with sleep loss and circadian misalignment.

Non-NASA Center↗

Circadian variation of EEG power spectra in NREM and REM sleep in humans: dissociation from body temperature

In humans, EEG power spectra in REM and NREM sleep, as well as characteristics of sleep spindles such as their duration, amplitude, frequency and incidence, vary with circadian phase. Recently it has been hypothesized that circadian variations in EEG spectra in humans are caused by variations in brain or body temperature and may not represent phenomena relevant to sleep regulatory processes. To test this directly, a further analysis of EEG power spectra - collected in a forced desynchrony protocol in which sleep episodes were scheduled to a 28-h period while the rhythms of body temperature and plasma melatonin were oscillating at their near 24-h period - was carried out. EEG power spectra were computed for NREM and REM sleep occurring between 90-120 and 270-300 degrees of the circadian melatonin rhythm, i.e. just after the clearance of melatonin from plasma in the 'morning' and just after the 'evening' increase in melatonin secretion. Average body temperatures during scheduled sleep at these two circadian phases were identical (36.72 degrees C). Despite identical body temperatures, the power spectra in NREM sleep were very different at these two circadian phases. EEG activity in the low frequency spindle range was significantly and markedly enhanced after the evening increase in plasma melatonin as compared to the morning phase. For REM sleep, significant differences in power spectra during these two circadian phases, in particular in the alpha range, were also observed. The results confirm that EEG power spectra in NREM and REM sleep vary with circadian phase, suggesting that the direct contribution of temperature to the circadian variation in EEG power spectra is absent or only minor, and are at variance with the hypothesis that circadian variations in EEG power spectra are caused by variations in temperature.

Non-NASA Center↗

Deblurring

In most instances, traditional EEG methodology provides insufficient spatial detail to identify relationships between brain electrical events and structures and functions visualized by magnetic resonance imaging or positron emission tomography. This article describes a method called Deblurring for increasing the spatial detail of the EEG and for fusing neurophysiologic and neuroanatomic data. Deblurring estimates potentials near the outer convexity of the cortex using a realistic finite element model of the structure of a subject's head determined from their magnetic resonance images. Deblurring is not a source localization technique and thus makes no assumptions about the number or type of generator sources. The validity of Deblurring has been initially tested by comparing deblurred data with potentials measured with subdural grid recordings. Results suggest that deblurred topographic maps, registered with a subject's magnetic resonance imaging and rendered in three dimensions, provide better spatial detail than has heretofore been obtained with scalp EEG recordings. Example results are presented from research studies of somatosensory stimulation, movement, language, attention and working memory. Deblurred ictal EEG data are also presented, indicating that this technique may have future clinical application as an aid to seizure localization and surgical planning.

Non-NASA Center↗

Effects of subfornical organ lesions on acutely induced thirst and salt appetite

We examined the role of the subfornical organ (SFO) in stimulating thirst and salt appetite using two procedures that initiate water and sodium ingestion within 1-2 h of extracellular fluid depletion. The first procedure used injections of a diuretic (furosemide, 10 mg/kg sc) and a vasodilator (minoxidil, 1-3 mg/kg ia) to produce hypotension concurrently with hypovolemia. The resulting water and sodium intakes were inhibited by intravenous administration of ANG II receptor antagonist (sarthran, 8 micrograms . kg(-1). min(-1)) or angiotensin-converting enzyme inhibitor (captopril, 2.5 mg/h). The second procedure used injections of furosemide (10 mg/kg sc) and a low dose of captopril (5 mg/kg sc) to initiate water and sodium ingestion upon formation of ANG II in the brain. Electrolytic lesions of the SFO greatly reduced the water intakes, and nearly abolished the sodium intakes, produced by these relatively acute treatments. These results contrast with earlier findings showing little effect of SFO lesions on sodium ingestion after longer-term extracellular fluid depletion.

NASA Discipline Regulatory Physiology↗

Inertial processing of vestibulo-ocular signals

New evidence for a central resolution of gravito-inertial signals has been recently obtained by analyzing the properties of the vestibulo-ocular reflex (VOR) in response to combined lateral translations and roll tilts of the head. It is found that the VOR generates robust compensatory horizontal eye movements independent of whether or not the interaural translatory acceleration component is canceled out by a gravitational acceleration component due to simultaneous roll-tilt. This response property of the VOR depends on functional semicircular canals, suggesting that the brain uses both otolith and semicircular canal signals to estimate head motion relative to inertial space. Vestibular information about dynamic head attitude relative to gravity is the basis for computing head (and body) angular velocity relative to inertial space. Available evidence suggests that the inertial vestibular system controls both head attitude and velocity with respect to a gravity-centered reference frame. The basic computational principles underlying the inertial processing of otolith and semicircular canal afferent signals are outlined.

NASA Discipline Neuroscience↗

Anteroventral third ventricle (AV3V) lesions alter c-fos expression induced by salt loading

Lesion of the anteroventral third-ventricle region (AV3VX) reduced saline consumption. Salt loading in AV3VX rats resulted in reduced but not completely abolished c-fos expression in the supraoptic and paraventricular nuclei. Intrinsic osmosensitivity of the magnocellular neurons, or input from other brain areas, such as the subfornical and median preoptic nuclei, may account for this residual c-fos expression. These regions showed c-fos expression following salt loading. Copyright 1999 Elsevier Science B.V.

Non-NASA Center↗

Evaluation of pGL1-TNF-alpha therapy in combination with radiation

Long-term control of high-grade brain tumors is rarely achieved with current therapeutic regimens. In this study a new plasmid-based human tumor necrosis factor-alpha (TNF-alpha) expression vector was synthesized (pGL1-TNF-alpha) and evaluated together with radiation in the aggressive, rapidly growing C6 rat glioma model. pGL1-TNF-alpha was successfully transfected into C6 cells in vitro using a cationic polyamine method. Expression was detected up to 7 days and averaged 0.4 ng of TNF-alpha in the culture medium from 1x10(5) cells. The expressed protein was biologically functional, as evidenced by growth inhibition of L929, a TNF-alpha-susceptible cell line. Using fluorescence-labeled monoclonal antibodies and laser scanning cytometry, we confirmed that both the P55 and P75 receptors for TNF-alpha were present on the C6 cell membrane. However, the receptors were present at low density and P55 was expressed more than the P75 receptor. These findings were in contrast to results obtained with TNF-alpha-susceptible L929 cells. Tests in athymic mice showed that pGL1-TNF-alpha administered intratumorally 16-18 h before radiation (each modality given three times) significantly inhibited C6 tumor progression (P<0.05). This effect was more than additive, because pGL1-TNF-alpha alone did not slow tumor growth and radiation alone had little effect on tumor growth. These results indicate that pGL1-TNF-alpha has potential to augment the antitumor effects of radiation against a tumor type that is virtually incurable.

Non-NASA Center↗

Correlation of Fos expression and circling asymmetry during gerbil vestibular compensation

Vestibular compensation is a central nervous system process resulting in recovery of functional movement and control following a unilateral vestibular lesion. Small pressure injections of phosphorothioate 20mer oligonucleotides were used to probe the role of the Fos transcription protein during vestibular compensation in the gerbil brainstem. During isoflurane gas anesthesia, antisense probes against the c-fos mRNA sequence were injected into the medial vestibular and prepositus nuclei unilaterally prior to a unilateral surgical labyrinthectomy. Anionic dyes, which did not interact with the oligonucleotides, were used to mark the injection site and help determine the extent of diffusion. The antiFos oligonucleotide injections reduced Fos expression at the injection site in neurons which normally express Fos after the lesion, and also affected circling behavior induced by hemilabyrinthectomy. With both ipsilateral and contralateral medial vestibular and prepositus nuclei injections, less ipsilateral and more contralateral circling was noted in animals injected with antiFos injections as compared to non-injected controls. The degree of change in these behaviors was dependent upon the side of the injection. Histologically, antiFos injections reduced the number of Fos immunolabeled neurons around the injection site, and increased Fos expression contralaterally. The correlation of the number of neurons with Fos expression to turning behavior was stronger for contralateral versus ipsilateral turns, and for neurons in the caudal and ipsilateral sub-regions of the medial vestibular and prepositus nuclei. The results are discussed in terms of neuronal firing activity versus translational activity based on the asymmetrical expression of the Fos inducible transcription factor in the medial vestibular and prepositus nuclei. Although ubiquitous in the brain, transcription factors like Fos can serve localized and specific roles in sensory-specific adaptive stimuli. Antisense injections can be an effective procedure for localized intervention into complex physiological functions, e.g. vestibular compensation. Copyright 1999 Elsevier Science B.V.

NASA Discipline Neuroscience↗

Characterization of ionic currents of cells of the subfornical organ that project to the supraoptic nuclei

The subfornical organ (SFO) is a forebrain structure that converts peripheral blood-borne signals reflecting the hydrational state of the body to neural signals and then through efferent fibers conveys this information to several central nervous system structures. One of the forebrain areas receiving input from the SFO is the supraoptic nucleus (SON), a source of vasopressin synthesis and control of release from the posterior pituitary. Little is known of the transduction and transmission processes by which this conversion of systemic information to brain input occurs. As a step in elucidating these mechanisms, the present study characterized the ionic currents of dissociated cells of the SFO that were identified as neurons that send efferents to the SON. A retrograde tracer was injected into the SON area in eleven-day-old rats. After three days for retrograde transport of the label, the SFOs of these animals were dissociated and plated for tissue culture. The retrograde tracer was used to identify the soma of SFO cells projecting to the SON so that voltage-dependent ionic currents using whole-cell voltage clamp methods could be studied. The three types of currents in labeled SFO neurons were characterized as a 1) rapid, transient inward current that can be blocked by tetrodotoxin (TTX) characteristic of a sodium current; 2) slow-onset sustained outward current that can be blocked by tetraethylammonium (TEA) characteristic of a delayed rectifier potassium current; and 3) remaining outward current that has a rapid-onset and transient characteristic of a potassium A-type current. Copyright 1999 Elsevier Science B.V.

Non-NASA Center↗

Multiple receptor subtypes mediate the effects of serotonin on rat subfornical organ neurons

The subfornical organ (SFO) receives significant serotonergic innervation. However, few reports have examined the functional effects of serotonin on SFO neurons. This study characterized the effects of serotonin on spontaneously firing SFO neurons in the rat brain slice. Of 31 neurons tested, 80% responded to serotonin (1-100 microM) with either an increase (n = 15) or decrease (n = 10) in spontaneous activity. Responses to serotonin were dose dependent and persisted after synaptic blockade. Excitatory responses could also be mimicked by the 5-hydroxytryptamine (5-HT)2A/2C receptor agonist 2,5-dimethoxy-4-iodoamphetamine (DOI; 1-10 microM) and could be blocked by the 5-HT2A/2C-receptor antagonist LY-53,857 (10 microM). LY-53,857 unmasked inhibitory responses to serotonin in 56% of serotonin-excited cells tested. Serotonin-inhibited cells were also inhibited by the 5-HT1A-receptor agonist 8-hydroxy-2(di-n-propylamino)tetralin (8-OH-DPAT; 1-10 microM; n = 7). The data indicate that SFO neurons are responsive to serotonin via postsynaptic activation of multiple receptor subtypes. The results suggest that excitatory responses to serotonin are mediated by 5-HT2A or 5-HT2C receptors and that inhibitory responses may be mediated by 5-HT1A receptors. In addition, similar percentages of serotonin-excited and -inhibited cells were also sensitive to ANG II. As such the functional relationship between serotonin and ANG II in the SFO remains unclear.

Non-NASA Center↗