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Biomedical subjects

S Inoué

Publications and source records attributed to S Inoué.

At least 19 recordsLinked to original sources
PubMed2005

Brain oxidation is an initial process in sleep induction.

CNS activity is generally coupled to the vigilance state, being primarily active during wakefulness and primarily inactive during deep sleep. During periods of high neuronal activity, a significant volume of oxygen is used to maintain neuronal membrane potentials, which subsequently produces cytotoxic reactive oxygen species (ROS). Glutathione, a major endogenous antioxidant, is an important factor protecting against ROS-mediated neuronal degeneration. Glutathione has also been proposed to be a sleep-promoting substance, yet the relationship between sleep and cerebral oxidation remains unclear. Here we report that i.c.v. infusion of the organic peroxide t-butyl-hydroperoxide at a concentration below that triggering neurodegeneration (0.1 micromol/100 microl/10 h) promotes sleep in rats. Also, microinjection (2 nmol, 2 microl) or microdialysis (100 microM, 20 min) of t-butyl-hydroperoxide into the preoptic/anterior hypothalamus (POAH) induces the release of the sleep-inducing neuromodulators, nitric oxide and adenosine, without causing neurodegeneration. Nitric oxide and adenosine release was inhibited by co-dialysis of the N-methyl-D-aspartate receptor antagonist, d(-)-2-amino-5-phosphonopentanoic acid (D-AP5; 1 mM), suggesting that glutamate-induced neuronal excitation mediates the peroxide-induced release of nitric oxide and adenosine. Indeed, Ca2+ release from mitochondria and delayed-onset Ca2+ influx via N-methyl-D-aspartate receptors was visualized during peroxide exposure using Ca2+ indicator proteins (YC-2.1 and mitochondrial-targeted Pericam) expressed in organotypic cultures of the POAH. In the in vitro models, t-butyl-hydroperoxide (50 microM) causes dendritic swelling followed by the intracellular Ca2+ mobilization, and D-AP5 (100 microM) or glutathione (500 microM) inhibited t-butyl-hydroperoxide-induced intracellular Ca2+ mobilization and protected POAH neurons from oxidative stress. These data suggest that low-level subcortical oxidation under the control of an antioxidant system may trigger sleep via the Ca(2+)-dependent release of sleep-inducing neuromodulators in the POAH, and thus we propose that a moderate increase of ROS during wakefulness in the neuronal circuits regulating sleep may be an initial trigger in sleep induction.

Adenosine↗
PubMed2001

Sleep-promoting activity of prolactin-releasing peptide (PrRP) in the rat.

The present study examines whether or not prolactin-releasing peptide (PrRP) infused intracerebroventricularly (i.c.v.) affects sleep and the release of prolactin (PRL) and growth hormone (GH) in rats. At a dose of 0.1 nmol, PrRP promoted rapid-eye-movement (REM) sleep, whereas 1.0 nmol increased both non-REM and REM sleep and 10.0 nmol enhanced only non-REM sleep. During the i.c.v. infusion of PrRP with 0.1 nmol, levels of plasma PRL were elevated, but GH levels were significantly decreased. Since it is reported that PrRP fails to induce PRL release from the male pituitary, the stimulatory effects of PrRP on PRL release observed here seem to be indirect. However, PRL stimulated by i.c.v.-infused PrRP could take part in the REM sleep-promoting activity of PrRP.

Animals↗
PubMed2001

A mechanism for nuclear positioning in fission yeast based on microtubule pushing.

The correct positioning of the nucleus is often important in defining the spatial organization of the cell, for example, in determining the cell division plane. In interphase Schizosaccharomyces pombe cells, the nucleus is positioned in the middle of the cylindrical cell in an active microtubule (MT)-dependent process. Here, we used green fluorescent protein markers to examine the dynamics of MTs, spindle pole body, and the nuclear envelope in living cells. We find that interphase MTs are organized in three to four antiparallel MT bundles arranged along the long axis of the cell, with MT plus ends facing both the cell tips and minus ends near the middle of the cell. The MT bundles are organized from medial MT-organizing centers that may function as nuclear attachment sites. When MTs grow to the cell tips, they exert transient forces produced by plus end MT polymerization that push the nucleus. After an average of 1.5 min of growth at the cell tip, MT plus ends exhibit catastrophe and shrink back to the nuclear region before growing back to the cell tip. Computer modeling suggests that a balance of these pushing MT forces can provide a mechanism to position the nucleus at the middle of the cell.

Cell Cycle↗
PubMed2001

The sulphydryl reagent, N-ethylmaleimide, disrupts sleep and blocks A1 adenosine receptor-mediated inhibition of intracellular calcium signaling in the in vitro ventromedial preoptic nucleus.

To explore the neuronal signaling mechanisms underlying sleep regulation in the rat, the present study examined continuous intra-third ventricle infusion of N-ethylmaleimide (NEM), a sulphydryl reagent that inhibits G(i/o) protein-coupled receptor-mediated signaling pathways. The diurnal infusion of NEM (0.01-10 micromol/10 h) dose-dependently inhibited both non-rapid eye movement sleep and rapid eye movement sleep. A maximal dose of NEM (10 micromol/10 h) dramatically inhibited day-time sleep (-57% for non-rapid eye movement sleep and -89% for rapid eye movement sleep) with a compensatory increase of sleep during the subsequent night-time (+33% for non-rapid eye movement sleep and +259% for rapid eye movement sleep). The day-time brain temperature was also increased by NEM, demonstrating effects of NEM on both sleep and body temperature levels. Immunostaining of the rat hypothalamus with a monoclonal antibody against the A1 adenosine receptor (A1R) was used to explore the distribution of a sleep-related G(i/o) protein-coupled receptor. Robust A1R-like immunoreactivity was found in the ventromedial preoptic nucleus and the supraoptic nucleus. Fura-2-based Ca(2+) imaging analysis of acute hypothalamic slices further demonstrated that the A1R agonist N(6)-cyclopentyladenosine (CPA; 200 nM) inhibited spontaneous Ca(2+) oscillations and high potassium (80 mM)-induced Ca(2+) flux in the ventromedial preoptic nucleus, while NEM (100-300 microM) and an A1R antagonist 8-cyclopentyl-dipropylxanthine (300 nM) blocked the CPA actions and increased the high potassium-induced Ca(2+) flux. From these results we suggest that NEM-sensitive G protein-coupled receptor(s) may play an important role in the regulation of sleep and body temperature in the rat and one possible mechanism is an A1R-mediated regulation of intracellular Ca(2+) concentrations in the ventromedial preoptic nucleus.

Adenosine↗
PubMed2001

Centrifuge polarizing microscope. I. Rationale, design and instrument performance.

We first describe early uses of the centrifuge for deciphering physical properties and molecular organization within living cells, as well as the development and use of centrifuge microscopes for such studies. The rationale for developing a centrifuge microscope that allows high-extinction polarized light microscopy to observe dynamic fine structures in living cells is next discussed. We then describe a centrifuge polarizing microscope (CPM) that we developed for observing fine structural changes in living cells which are being exposed to up to approximately 11 500 times earth's gravitational field (g). With the specimen housed in a rotor supported on an air spindle motor, and imaged through an external microscope illuminated by a precisely synchronized flash of less than 10 ns duration from a Nd:YAG laser, the image of the spinning object remains steady up to the maximum speed of 11 700 rev min-1, or up to approximately 11 500 x g. The image is captured, at up to 25 frames s-1, by an interference-fringe-free CCD camera that is synchronized to the centrifuge rotor. At all speeds (in 100 rev min-1 increments), the image is resolved to better than 1 microm, while birefringence of the specimen, housed in a specially designed specimen chamber that suffers low-stress birefringence and prevents leakage of the physiological solutions, is detected with a retardance sensitivity of better than 1 nm. Differential interference contrast and fluorescence images (532 nm excitation) of the spinning specimen can also be generated with the CPM. The second part of this study (Inoué et al., J. Microsc. 201 (2001) 357-367, describes several biological applications of the CPM that we have explored. Individual live cells, such as oocytes and blood cells, are supported on a sucrose or Percoll density gradient while other cells, such as cultured fibroblasts and Dictyostelium amoebae, are observed crawling on glass surfaces. Observations of these cells exposed to the high G fields (centripetal acceleration/g) in the CPM are yielding many new results that lead to intriguing questions regarding the organization and function of fine structures in living cells and related quasi-fluid systems.

Animals↗
PubMed2001

Centrifuge polarizing microscope. II. Sample biological applications.

The rationale, design and general performance of the CPM (centrifuge polarizing microscope) were described in Part I of this study (Inoué et al. J. Microsc. 201 (2001) 341-356. In this second part, we describe observations on several biological samples that we have explored over the past two years using the CPM. As described in the first part of the study, although the CPM was basically designed as a high-extinction centrifuge polarizing microscope, it also allows observations of the specimen exposed to high centrifugal fields up to 10 500 x g (earth's gravitational acceleration) in fluorescence (532-nm excitation) and in DIC (differential interference or Nomarski contrast).

Anemia, Sickle Cell↗
PubMed2001

Spatio-temporal EEG power spectral patterns during a short daytime nap.

This is an approach to investigate topographic changes in electroencephalographic (EEG) spectral power during pre- and post-nap wakefulness as well as stages 1 (S1) and 2 (S2) NREM sleep in 12 subjects. Delta- and theta-band power significantly increased in the frontal and central regions during S1 and S2 with an increase in inter- and intra-hemispheric correlations. Beta-band power significantly increased in the frontal, central and parietal regions during S2 with an increase in interhemispheric correlation. In contrast, alpha-band power significantly decreased in the parietal-occipital regions during S1 and S2 with a decrease in interhemispheric correlation. Thus, daytime nap modulated spatio-temporal patterns of EEG power spectral patterns in wide scalp regions.

Adult↗
PubMed2000

How well can an amoeba climb?

We report here our efforts to measure the crawling force generated by cells undergoing amoeboid locomotion. In a centrifuge microscope, acceleration was increased until amoebae of Dictyostelium discoideum were "stalled" or no longer able to "climb up." The "apparent weight" of the amoebae at stalling rpm in myosin mutants depended on the presence of myosin II (but not myosins IA and IB) and paralleled the cortical strength of the cells. Surprisingly, however, the cell stalled not only in low-density media as expected but also in media with densities greater than the cell density where the buoyant force should push the amoeba upward. We find that the leading pseudopod is bent under centrifugal force in all stalled amoebae, suggesting that this pseudopod is very dense indeed. This finding also suggests that directional cell locomotion against resistive forces requires a turgid forward-pointing pseudopod, most likely sustained by cortical actomyosin II.

Amoeba↗
PubMed2000

Continuous exposure to dim illumination uncouples temporal patterns of sleep, body temperature, locomotion and drinking behavior in the rat.

Dissociable circadian rhythms of sleep and body temperature in primates are thought to be regulated by independent oscillators whereas the uncoupling of circadian rhythms has not been well described in other mammals. Therefore, we made simultaneous recordings of non-rapid-eye-movement-sleep (NREMS), rapid-eye-movement-sleep (REMS), brain temperature, intraperitoneal temperature, locomotion and drinking activity under light-dark (LD) and continuous dim illumination (dim LL) and analyzed their interrelations. The rhythmic patterns of body temperature, locomotion and drinking were modified on the 12th circadian day of dim LL, while the mean body temperature as well as mean occurrence of drinking and locomotor activities did not change significantly. In contrast, dim LL exposure significantly increased the total time spent in NREMS during the resting phase of dim LL and increased REMS episodes during the active phase of dim LL. The diverse effects of dim LL exposure on the recorded phenomena suggest that temporal patterns of sleep were the most sensitive to perturbations of lighting and that differential oscillatory mechanisms may regulate sleep and other circadian rhythms in the rat.

Animals↗
PubMed2000

Strong rebound of wakefulness follows prostaglandin D2- or adenosine A2a receptor agonist-induced sleep.

We studied the effect of sleep excess on the sleep-wakefulness pattern of rats. Subarachnoid infusion of prostaglandin D2 or the adenosine A2a receptor agonist CGS21680 effectively induced slow wave sleep (SWS) for the first 12 h of the night-time period, whereas they did not induce sleep during the following 24 h of infusion. An increase in the amount of wakefulness was seen during the last 12 h of prostaglandin D2 infusion. The amounts of wakefulness strongly increased during the following 36-h recovery period. Rebound wakefulness was extraordinarily strong after the cessation of CGS21680 infusion, reaching almost complete insomnia during the night-time. Treatment of animals with prostaglandin D2 overnight, following by treatment with CGS21680 on the next night, resulted in the strongest induction of wakefulness rebound. During the rebound period, the amount of wakefulness reached up to 50 min per hour in the daytime. Rebound of wakefulness depended on the amounts of preceding SWS induced by infusion of prostaglandin D2 for 6 or 12 h and of CGS21680 for 12 h. The larger the amount of SWS, the larger the amount of the following rebound of wakefulness. Rebounds of wakefulness occurred as a result of decrease in SWS amounts, whereas paradoxical sleep amounts did not change. Desensitization of adenosine A2a receptors and accumulation of prostaglandin E2 may be involved in the production of strong wakefulness rebound following relatively long treatments (more than 12 h) with prostaglandin D2 or CGS21680.

Adenosine↗
PubMed2000

A short daytime nap modulates levels of emotions objectively evaluated by the emotion spectrum analysis method.

A novel objective technique, the emotion spectrum analysis method, was first applied to investigate emotional fluctuations before, during and after a daytime nap in eight healthy young adults (four males and four females). The subjects were allowed to freely nap between 13.00 and 14.00 h, in which stages 1 and 2 non-rapid eye movement sleep occurred on average for 5.9 and 20.8 min, respectively. Emotional components such as anger, joy, relaxation and sadness were numerically estimated on the basis of spatio-temporal behavior of 21-channel electroencephalogram and analyzed statistically. In comparison with the prenap waking level, the magnitudes of the anger, joy and relaxation components remained stably unchanged during the nap but elevated significantly during the postnap waking period. The sadness component exhibited little significant change throughout the observation period. From the results, we suggest that a short daytime nap modulates the emotions to improve the postnap mental states.

Adaptation, Psychological↗
PubMed2000

Effects of prolactin-releasing peptide (PrRP) on sleep regulation in rats.

The present study examined in rats how prolactin-releasing peptide (PrRP), a new hypothalamic hormone, infused centrally during the dark period affects sleep and plasma levels of prolactin (PRL). At a dose of 0.1 nmol, PrRP increased only rapid eye movement (REM) sleep, whereas with 1.0 nmol both non-REM sleep and REM sleep were enhanced. However, 10.0 nmol of PrRP increased only non-REM sleep with a febrile response. The levels of plasma PRL were elevated during the infusion of PrRP with 0.1 and 1.0 nmol. Consequently, the increased release of PRL correlated with significant increases in REM sleep, but not in non-REM sleep.

Animals↗
PubMed2000

Effects of aniracetam on impaired sleep patterns in stroke-prone spontaneously hypertensive rats.

The aim of the present study was to determine the pattern of sleep disturbances and the effects on sleep of aniracetam, a cognitive enhancer, in stroke-prone spontaneously hypertensive rats (SHRSP). Compared with normotensive control rats, SHRSP exhibited an impaired sleep pattern characterized by suppressed diurnal rapid eye movement (REM) sleep and excessive nocturnal non-REM sleep. At a dose of 30 mg/kg per day p.o., aniracetam increased REM sleep in the light period after administration for 5 consecutive days. Consequently, suppressed REM sleep in SHRSP was restored by repeated treatment with aniracetam. Aniracetam could be useful in improving REM sleep impairment associated with vascular dementia.

Animals↗